The key issue of block-based multi-focus image fusion is to determine the size of the sub-block because different sizes of the sub-block will lead to different fusion effects. To solve this problem, this paper presents a novel genetic algorithm (GA) based multi-focus image fusion method, in which the block size can be automatically found. In our method, the Sum-modified-Laplacian (SML) is selected as an evaluation criterion to measure the clarity of the image sub-block, and the edge information retention is employed to calculate the fitness of each individual. Then, through the selection, crossover and mutation procedures of the GA, we can obtain the optimal solution for the sub-block, which is finally used to fuse the images. Experimental results show that the proposed method outperforms the traditional methods, including the average, gradient pyramid, discrete wavelet transform (DWT), shift invariant DWT (SIDWT) and two existing GA-based methods in terms of both the visual subjective evaluation and the objective evaluation.