Multimodal image registration is a key for many clinical image‐guided interventions. However, it is a challenging task because of complicated and unknown relationships between different modalities. Currently, deep supervised learning is the state‐of‐theart method at which the registration is conducted in end‐to‐end manner and one‐shot. Therefore, a huge ground‐truth data is required to improve the results of deep neural networks for registration. Moreover, supervised methods may yield models that bias towards annotated structures. Here, to deal with above challenges, an alternative approach is using unsupervised learning models. In this study, we have designed a novel deep unsupervised Convolutional Neural Network (CNN)‐based model based on computer tomography/magnetic resonance (CT/MR) co‐registration of brain images in an affine manner. For this purpose, we created a dataset consisting of 1100 pairs of CT/MR slices from the brain of 110 neuropsychic patients with/without tumor. At the next step, 12 landmarks were selected by a well‐experienced radiologist and annotated on each slice resulting in the computation of series of metrics evaluation, target registration error (TRE), Dice similarity, Hausdorff, and Jaccard coefficients. The proposed method could register the multimodal images with TRE 9.89, Dice similarity 0.79, Hausdorff 7.15, and Jaccard 0.75 that are appreciable for clinical applications. Moreover, the approach registered the images in an acceptable time 203 ms and can be appreciable for clinical usage due to the short registration time and high accuracy. Here, the results illustrated that our proposed method achieved competitive performance against other related approaches from both reasonable computation time and the metrics evaluation.