This work aims to achieve the 6000t compression-shear test machine frame design with the lightweight. The force condition of the compression-shear test machine frame under limited working conditions is first analyzed, and the static analysis of the compression-shear test machine frame is performed using ABAQUS. Then, taking the volume of the frame of the compression-shear testing machine as the constraint condition, the topology optimization of the compression-shear testing machine frame is performed using the variable density method of topology optimization, and the model is reconstructed accordingly. Finally, not only the static characteristics of the frame before and after optimization but also the modal characteristics of the frame before and after optimization and the dynamic characteristics after sudden unloading are compared and analyzed. The results show that the weight of the frame decreases by 14.5% after optimization, and the maximum static stress of the frame is still less than the yield strength of the material; the maximum displacement is still less than the allowable maximum displacement, which meets the requirements of static strength and stiffness. The natural frequency of each mode is much greater than the working frequency, which meets the requirements of dynamic stiffness. After sudden unloading, the maximum dynamic stress of beams, columns, and base of the frame are less than the yield strength of materials, which meets the requirements of dynamic strength.