Aiming at the problem of heavy press body and waste of materials, for EP-12500 heavy-duty electric CNC screw press body, the method of lightweight design for press body structure was explored. Firstly, the finite element analysis on the press body was conducted based on Workbench, and the non-bear zone where the stress value of press body was far less than the yield strength of material was obtained. Then, the non-bear zone of press body was topologically optimized by topology optimization modules. Finally, with the goal of minimizing the mass, the specific position of material removal for the press body structure was determined to realize the lightweight design of press body structure. The optimization results show that the volume and mass of press body are reduced by 9.65% after optimization, which realizes the lightweight of press body and reduces the manufacturing cost. The maximum deformation amount of press body under the preloading condition is increased by 0.17 mm, and the maximum deformation amount under the striking condition is increased by less than 0.01 mm, which is basically consistent with the original press body deformation. The vertical stiffness of press body under the preloading condition is 8.21 MN·mm-1 , and the vertical stiffness under the striking condition is 13.08 MN·mm-1, which all meet the use requirements. The maximum equivalent stress of press body under the preloading condition is reduced by 2.51%, and the maximum equivalent stress under  the striking condition is reduced by 18.3%, which reduces the impact force borne by the base and improves the service life of base.