In order to optimize the design of modular sprocket shaft and determine the impact of key design variables on the overall stress of the design scheme. Using simulation analysis software to calculate the design variable combination scheme arranged by the experimental design software, and using response surface method (RSM) to analyze the interaction between various influencing factors, a three-dimensional spatial response surface is constructed to obtain an optimized design variable combination. The simulation of the optimized scheme shows that its stress is basically consistent with the results calculated by the fitting equation, and the overall stress is more balanced.