Abstract: A fluorescence molecular tomography reconstruction method includes: obtaining an MPI three-dimensional tomographic image, a body surface near-infrared fluorescence two-dimensional image, and a CT image; constructing an SIS capable of accommodating the ROI, and discretizing the SIS by using a finite element method; performing data mapping to obtain detected surface fluorescence signals, a prior of the anatomical structure of tissues and organs around the tumor and a prior of the tumor; performing forward model calculation to obtain a system matrix and constructing an objective function; iteratively solving the objective function based on the Laplacian regularization matrix to obtain a fluorescence molecular tomography reconstruction result; the present invention adopts MPI to guide the FMT, achieving complete morphology and structure, clear tissue edges, and high accuracy of spatial position.