In this paper,the mechanical properties of a certain type of CNC lathe spindle box are analyzed by the finite element software HyperWorks. On this basis, the topology optimization of the CNC lathe spindle box is done by the variable density method. where the spindle box relative density is taken as the design variable and the minimum volume of the spindle box as the objective function, its static deformation and the low modes as constraints．That is to find the optimal layout of the structure,and then the size optimization of the spindle box is done to make further amendments of the topology optimization results. This design method achieves the lightweight design of the spindle box, reduces manufacturing costs,and provides a theoretical basis for enterprises to improve the structure of CNC lathe spindle box.