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In order to overcome the poor robustness of traditional image registration algorithms in illuminating and solving the problem of low accuracy of a learning-based image homography matrix estimation algorithm, an image registration algorithm based on convolutional neural network (CNN) and local homography transformation is proposed. Firstly, to ensure the diversity of samples, a sample and label generation method based on moving direct linear transformation (MDLT) is designed. The generated samples and labels can effectively reflect the local characteristics of images and are suitable for training the CNN model with which multiple pairs of local matching points between two images to be registered can be calculated. Then, the local homography matrices between the two images are estimated by using the MDLT and finally the image registration can be realized. The experimental results show that the proposed image registration algorithm achieves higher accuracy than other commonly used algorithms such as the SIFT, ORB, ECC, and APAP algorithms, as well as another two learning-based algorithms, and it has good robustness for different types of illumination imaging.