Fluorescence molecular tomography (FMT) has been widely used in preclinical tumor imaging, which enables three-dimensional imaging of the distribution of fluorescent probes in small animal bodies via image reconstruction method. However, the reconstruction results are usually unsatisfactory in the term of robustness and efficiency because of the ill-posed and ill-conditioned of FMT problem. In this study, an FMT reconstruction method based on primal accelerated proximal gradient (PAPG) descent and L1-norm regularized projection (L1RP) is proposed. The proposed method utilizes the current and previous iterations to obtain a search point at each iteration. To achieve fast convergence, the PAPG method is applied to efficiently solve the search point, and then L1RP is performed to obtain the robust and accurate reconstruction. To verify the performance of the proposed method, simulation experiments are conducted. The comparative results revealed that it held advantages of robustness, accuracy, and efficiency in FMT reconstructions. Furthermore, a phantom experiment and an in vivo mouse experiment were also performed, which proved the potential and feasibility of the proposed method for practical applications. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE).