Abstract: In this paper, a set of mathematical model for main PUREX process based on mixer-settler(MPMS) is constructed by establishing distribution ratio model, chemical reaction model with specific algorithm, and mass transfer model, using for calculating substances’ concentration of each stage of mixer-settler. By comparing the simulation results and experiment results of two representative PUREX process, it indicates that there is good accuracy of our mathematical model. MPMS will be useful for PUREX process simulation based on multi-stage mixer-settler.