In order to optimize the structural performance of the independently developed six-axis three-planetary row hydraulic mechanical continuously variable transmission(HMCVT) box, the topology optimization was carried out to improve the utilization rate of materials and reduce the weight of the HMCVT box. Considering the complexity of the load on the HMCVT box, the transmission virtual prototype model was established based on the virtual prototype technology. Combined with the tractor ground vibration test, the dynamic load of transmission bearing hole is obtained under three different load transfer conditions of single planetary row, double planetary row and three planetary row, respectively. Secondly, with stress and volume ratio as constraints, a comprehensive objective function containing the stiffness and the first third order natural frequency of the box under three working conditions was established based on the compromise programming method. Then, considering the influence of sub-objective weight, the optimal weight was obtained based on proxy model and genetic algorithm and compared with traditional empirical method and analytic hierarchy process. Finally, the topology optimization of the HMCVT box was carried out by using Hypermesh. The optimization results show that the maximum stress of the optimized box is reduced by 13.6%, and the maximum deformation is reduced by 0.5%. The stiffness and strength of the box are basically unchanged or slightly improved, and the mass is reduced by 10.9%. It achieve the target of lightweight gearbox box.