diff --git a/docs/source/losses.rst b/docs/source/losses.rst
index d2c8e02ca4..462c303e65 100644
--- a/docs/source/losses.rst
+++ b/docs/source/losses.rst
@@ -65,3 +65,8 @@ Registration Losses
 ~~~~~~~~~~~~~~~~~~~
 .. autoclass:: BendingEnergyLoss
     :members:
+
+`LocalNormalizedCrossCorrelationLoss`
+~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+.. autoclass:: LocalNormalizedCrossCorrelationLoss
+    :members:
diff --git a/monai/losses/__init__.py b/monai/losses/__init__.py
index ae380a7182..ba6acafd47 100644
--- a/monai/losses/__init__.py
+++ b/monai/losses/__init__.py
@@ -22,4 +22,5 @@
     generalized_wasserstein_dice,
 )
 from .focal_loss import FocalLoss
+from .image_dissimilarity import LocalNormalizedCrossCorrelationLoss
 from .tversky import TverskyLoss
diff --git a/monai/losses/image_dissimilarity.py b/monai/losses/image_dissimilarity.py
new file mode 100644
index 0000000000..d42303e154
--- /dev/null
+++ b/monai/losses/image_dissimilarity.py
@@ -0,0 +1,159 @@
+# Copyright 2020 - 2021 MONAI Consortium
+# Licensed under the Apache License, Version 2.0 (the "License");
+# you may not use this file except in compliance with the License.
+# You may obtain a copy of the License at
+#     http://www.apache.org/licenses/LICENSE-2.0
+# Unless required by applicable law or agreed to in writing, software
+# distributed under the License is distributed on an "AS IS" BASIS,
+# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+# See the License for the specific language governing permissions and
+# limitations under the License.
+from typing import Union
+
+import torch
+from torch.nn import functional as F
+from torch.nn.modules.loss import _Loss
+
+from monai.networks.layers import gaussian_1d, separable_filtering
+from monai.utils import LossReduction
+
+
+def make_rectangular_kernel(kernel_size: int) -> torch.Tensor:
+    return torch.ones(kernel_size)
+
+
+def make_triangular_kernel(kernel_size: int) -> torch.Tensor:
+    fsize = (kernel_size + 1) // 2
+    if fsize % 2 == 0:
+        fsize -= 1
+    f = torch.ones((1, 1, fsize), dtype=torch.float).div(fsize)
+    padding = (kernel_size - fsize) // 2 + fsize // 2
+    return F.conv1d(f, f, padding=padding).reshape(-1)
+
+
+def make_gaussian_kernel(kernel_size: int) -> torch.Tensor:
+    sigma = torch.tensor(kernel_size / 3.0)
+    kernel = gaussian_1d(sigma=sigma, truncated=kernel_size // 2, approx="sampled", normalize=False) * (
+        2.5066282 * sigma
+    )
+    return kernel[:kernel_size]
+
+
+kernel_dict = {
+    "rectangular": make_rectangular_kernel,
+    "triangular": make_triangular_kernel,
+    "gaussian": make_gaussian_kernel,
+}
+
+
+class LocalNormalizedCrossCorrelationLoss(_Loss):
+    """
+    Local squared zero-normalized cross-correlation.
+    The loss is based on a moving kernel/window over the y_true/y_pred,
+    within the window the square of zncc is calculated.
+    The kernel can be a rectangular / triangular / gaussian window.
+    The final loss is the averaged loss over all windows.
+
+    Adapted from:
+        https://github.com/voxelmorph/voxelmorph/blob/legacy/src/losses.py
+        DeepReg (https://github.com/DeepRegNet/DeepReg)
+    """
+
+    def __init__(
+        self,
+        in_channels: int,
+        ndim: int = 3,
+        kernel_size: int = 9,
+        kernel_type: str = "rectangular",
+        reduction: Union[LossReduction, str] = LossReduction.MEAN,
+        smooth_nr: float = 1e-7,
+        smooth_dr: float = 1e-7,
+    ) -> None:
+        """
+        Args:
+            in_channels: number of input channels
+            ndim: number of spatial ndimensions, {``1``, ``2``, ``3``}. Defaults to 3.
+            kernel_size: kernel spatial size, must be odd.
+            kernel_type: {``"rectangular"``, ``"triangular"``, ``"gaussian"``}. Defaults to ``"rectangular"``.
+            reduction: {``"none"``, ``"mean"``, ``"sum"``}
+                Specifies the reduction to apply to the output. Defaults to ``"mean"``.
+
+                - ``"none"``: no reduction will be applied.
+                - ``"mean"``: the sum of the output will be divided by the number of elements in the output.
+                - ``"sum"``: the output will be summed.
+            smooth_nr: a small constant added to the numerator to avoid nan.
+            smooth_dr: a small constant added to the denominator to avoid nan.
+        """
+        super(LocalNormalizedCrossCorrelationLoss, self).__init__(reduction=LossReduction(reduction).value)
+        self.in_channels = in_channels
+
+        self.ndim = ndim
+        if self.ndim not in [1, 2, 3]:
+            raise ValueError(f"Unsupported ndim: {self.ndim}-d, only 1-d, 2-d, and 3-d inputs are supported")
+
+        self.kernel_size = kernel_size
+        if self.kernel_size % 2 == 0:
+            raise ValueError(f"kernel_size must be odd, got {self.kernel_size}")
+
+        if kernel_type not in kernel_dict.keys():
+            raise ValueError(
+                f'Unsupported kernel_type: {kernel_type}, available options are ["rectangular", "triangular", "gaussian"].'
+            )
+        self.kernel = kernel_dict[kernel_type](self.kernel_size)
+        self.kernel_vol = torch.sum(self.kernel) ** self.ndim
+        self.smooth_nr = float(smooth_nr)
+        self.smooth_dr = float(smooth_dr)
+
+    def forward(self, input: torch.Tensor, target: torch.Tensor) -> torch.Tensor:
+        """
+        Args:
+            input: the shape should be BNH[WD].
+            target: the shape should be BNH[WD].
+        Raises:
+            ValueError: When ``self.reduction`` is not one of ["mean", "sum", "none"].
+        """
+        assert (
+            input.shape[1] == self.in_channels
+        ), f"expecting input with {self.in_channels} channels, got input of shape {input.shape}"
+        assert (
+            input.ndim - 2 == self.ndim
+        ), f"expecting input with {self.ndim} spatial dimensions, got input of shape {input.shape}"
+        assert (
+            target.shape == input.shape
+        ), f"ground truth has differing shape ({target.shape}) from input ({input.shape})"
+
+        t2, p2, tp = target ** 2, input ** 2, target * input
+
+        # sum over kernel
+        t_sum = separable_filtering(target, kernels=[self.kernel] * self.ndim).sum(1, keepdim=True)
+        p_sum = separable_filtering(input, kernels=[self.kernel] * self.ndim).sum(1, keepdim=True)
+        t2_sum = separable_filtering(t2, kernels=[self.kernel] * self.ndim).sum(1, keepdim=True)
+        p2_sum = separable_filtering(p2, kernels=[self.kernel] * self.ndim).sum(1, keepdim=True)
+        tp_sum = separable_filtering(tp, kernels=[self.kernel] * self.ndim).sum(1, keepdim=True)
+
+        # average over kernel
+        t_avg = t_sum / self.kernel_vol
+        p_avg = p_sum / self.kernel_vol
+
+        # normalized cross correlation between t and p
+        # sum[(t - mean[t]) * (p - mean[p])] / std[t] / std[p]
+        # denoted by num / denom
+        # assume we sum over N values
+        # num = sum[t * p - mean[t] * p - t * mean[p] + mean[t] * mean[p]]
+        #     = sum[t*p] - sum[t] * sum[p] / N * 2 + sum[t] * sum[p] / N
+        #     = sum[t*p] - sum[t] * sum[p] / N
+        #     = sum[t*p] - sum[t] * mean[p] = cross
+        # the following is actually squared ncc
+        cross = tp_sum - p_avg * t_sum
+        t_var = t2_sum - t_avg * t_sum  # std[t] ** 2
+        p_var = p2_sum - p_avg * p_sum  # std[p] ** 2
+        ncc: torch.Tensor = (cross * cross + self.smooth_nr) / (t_var * p_var + self.smooth_dr)
+        # shape = (batch, 1, D, H, W)
+
+        if self.reduction == LossReduction.SUM.value:
+            return torch.sum(ncc).neg()  # sum over the batch and spatial ndims
+        if self.reduction == LossReduction.NONE.value:
+            return ncc.neg()
+        if self.reduction == LossReduction.MEAN.value:
+            return torch.mean(ncc).neg()  # average over the batch and spatial ndims
+        raise ValueError(f'Unsupported reduction: {self.reduction}, available options are ["mean", "sum", "none"].')
diff --git a/tests/test_local_normalized_cross_correlation_loss.py b/tests/test_local_normalized_cross_correlation_loss.py
new file mode 100644
index 0000000000..cb2f446dfc
--- /dev/null
+++ b/tests/test_local_normalized_cross_correlation_loss.py
@@ -0,0 +1,146 @@
+# Copyright 2020 MONAI Consortium
+# Licensed under the Apache License, Version 2.0 (the "License");
+# you may not use this file except in compliance with the License.
+# You may obtain a copy of the License at
+#     http://www.apache.org/licenses/LICENSE-2.0
+# Unless required by applicable law or agreed to in writing, software
+# distributed under the License is distributed on an "AS IS" BASIS,
+# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+# See the License for the specific language governing permissions and
+# limitations under the License.
+
+import unittest
+
+import numpy as np
+import torch
+from parameterized import parameterized
+
+from monai.losses.image_dissimilarity import LocalNormalizedCrossCorrelationLoss
+
+TEST_CASES = [
+    [
+        {"in_channels": 3, "ndim": 3, "kernel_size": 3, "kernel_type": "rectangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 2, "kernel_size": 3, "kernel_type": "rectangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 2, "kernel_size": 3, "kernel_type": "triangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 2, "kernel_size": 3, "kernel_type": "gaussian"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None].expand(1, 3, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 1, "kernel_size": 3, "kernel_type": "rectangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 1, "kernel_size": 3, "kernel_type": "triangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 1, "kernel_size": 3, "kernel_type": "gaussian"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(1, 3, 3),
+        },
+        -1.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 1, "kernel_size": 3, "kernel_type": "gaussian", "reduction": "sum"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(2, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None].expand(2, 3, 3),
+        },
+        -6.0,
+    ],
+    [
+        {"in_channels": 3, "ndim": 3, "kernel_size": 3, "kernel_type": "rectangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3) ** 2,
+        },
+        -0.06062524,
+    ],
+    [
+        {"in_channels": 3, "ndim": 3, "kernel_size": 5, "kernel_type": "triangular"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3) ** 2,
+        },
+        -0.923356,
+    ],
+    [
+        {"in_channels": 3, "ndim": 3, "kernel_size": 3, "kernel_type": "gaussian"},
+        {
+            "input": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3),
+            "target": torch.arange(0, 3, dtype=torch.float)[None, :, None, None, None].expand(1, 3, 3, 3, 3) ** 2,
+        },
+        -1.306177,
+    ],
+]
+
+
+class TestLocalNormalizedCrossCorrelationLoss(unittest.TestCase):
+    @parameterized.expand(TEST_CASES)
+    def test_shape(self, input_param, input_data, expected_val):
+        result = LocalNormalizedCrossCorrelationLoss(**input_param).forward(**input_data)
+        np.testing.assert_allclose(result.detach().cpu().numpy(), expected_val, rtol=1e-4)
+
+    def test_ill_shape(self):
+        loss = LocalNormalizedCrossCorrelationLoss(in_channels=3, ndim=3)
+        # in_channel unmatch
+        with self.assertRaisesRegex(AssertionError, ""):
+            loss.forward(torch.ones((1, 2, 3, 3, 3), dtype=torch.float), torch.ones((1, 2, 3, 3, 3), dtype=torch.float))
+        # ndim unmatch
+        with self.assertRaisesRegex(AssertionError, ""):
+            loss.forward(torch.ones((1, 3, 3, 3), dtype=torch.float), torch.ones((1, 3, 3, 3), dtype=torch.float))
+        # input, target shape unmatch
+        with self.assertRaisesRegex(AssertionError, ""):
+            loss.forward(torch.ones((1, 3, 3, 3, 3), dtype=torch.float), torch.ones((1, 3, 4, 4, 4), dtype=torch.float))
+
+    def test_ill_opts(self):
+        input = torch.ones((1, 3, 3, 3, 3), dtype=torch.float)
+        target = torch.ones((1, 3, 3, 3, 3), dtype=torch.float)
+        with self.assertRaisesRegex(ValueError, ""):
+            LocalNormalizedCrossCorrelationLoss(in_channels=3, kernel_type="unknown")(input, target)
+        with self.assertRaisesRegex(ValueError, ""):
+            LocalNormalizedCrossCorrelationLoss(in_channels=3, kernel_type=None)(input, target)
+        with self.assertRaisesRegex(ValueError, ""):
+            LocalNormalizedCrossCorrelationLoss(in_channels=3, kernel_size=4)(input, target)
+        with self.assertRaisesRegex(ValueError, ""):
+            LocalNormalizedCrossCorrelationLoss(in_channels=3, reduction="unknown")(input, target)
+        with self.assertRaisesRegex(ValueError, ""):
+            LocalNormalizedCrossCorrelationLoss(in_channels=3, reduction=None)(input, target)
+
+
+if __name__ == "__main__":
+    unittest.main()