Multimodality brain image registration technology is the key technology to determine the accuracy and speed of brain diagnosis and treatment. In order to achieve high-precision image registration, a fast subpixel registration algorithm based on single-step DFT combined with phase correlation constraint in multimodality brain image was proposed in this paper. Firstly, the coarse positioning at the pixel level was achieved by using the downsampling cross-correlation model, which reduced the Fourier transform dimension of the cross-correlation matrix and the multiplication of the discrete Fourier transform matrix, so as to speed up the coarse registration process. Then, the improved DFT multiplier of the matrix multiplication was used in the neighborhood of the coarse point, and the subpixel fast location was achieved by the bidirectional search strategy. Qualitative and quantitative simulation experiment results show that, compared with comparison registration algorithms, our proposed algorithm could greatly reduce space and time complexity without losing accuracy.