In order to improve the dynamic performance of infrared seeker′s stabilization platform and diminish the negative effect of vibration environment on the stabilized accuracy and image quality of electro-optical load, a topology optimization based on the variable density theory was studied. In the topology optimization of the main frame of infrared seeker′s stabilization platform, the maximum stiffness was taken as an objective function and the volume ratio constraint was taken as response functions by using the software of NX/TOSCA. The stiffness and modal performance of the main frame structure after optimization were analyzed by comparing with experience design. The results show that the mass of the main frame is reduced tremendously by 32.4% under the condition of the improved dynamic performance, the maximum deformation is reduced from 3.2 μm to 2.8 μm, and the first order natural frequency isimproved from 1 567 Hz to 1 953 Hz, that is beneficial to the lightweight level of ascension and the performance improved. Finally, the dynamic performance of the main frame is verified by vibration test and stabilized accuracy test, which proved the result of the topology optimization. This topology optimization method will provide help to structure design of the other important parts.