The work aims to propose an image registration method based on hybrid search algorithm, so as to improve the accuracy of printing image registration (IR). Firstly, the normalized mutual information of the image was calculated, and then the global search was done by GA (genetic algorithm) to obtain the rough registration parameters. Finally, the Powell algorithm was used for local optimization to obtain the precise registration parameters. Compared with the single Powell or GA search algorithm, the registration results of hybrid algorithm had smaller registration error in each geometric transformation direction. The proposed hybrid algorithm registration is much more accurate and fabulously faster than GA algorithm and Powell algorithm.