Aiming at the collaborative design challenge of stiffness, thermal stability and lightweight for the focal plane substrate structure in space telescopes, the topology optimization method is adopted to conduct optimization design. Taking the focal plane substrate structure of a large space telescope as the optimization object, a topological optimization mathematical model with dual objective functions of minimizing compliance and temperature gradient was established, and the analytic hierarchy process was employed to determine the weight coefficients of objectives. Subsequently, the COMSOL Multiphysics software was used for solution, and the topological optimization results of the substrate structure were obtained. Finally, the substrate structure was reconstructed based on the optimization results and validated through finite element simulation. The results demonstrated that compared with the original substrate, the optimized substrate achieved a 39.94% reduction in mass, a 4.92% decrease in maximum displacement, and a fundamental frequency of 801.2 Hz, thereby meeting design requirements and achieving the lightweight goal. The research results provide a reference for the lightweight design of other engineering structures.