Cable-stayed bridges have commonly been built for crossing large-span obstacles, such as rivers, valleys, and existing structures. Obtaining an optimum design for a cable-stayed bridge is challenging, due to the large number of design variables and design constraints that are typically nonlinear and usually conflict with each other. Therefore, it is a reasonable alternative to turn the large and complex optimization problem into two sub-problems, i.e., optimizing the internal force distribution by adjusting the cable prestressing forces, and optimizing the other sizing or geometrical parameters. However, conventional methods are lacking in efficiency when dealing with the problem of optimization of cable forces in the first sub-problem, under the circumstance that iteration between the two sub-problems is required. To address this, this paper presents a surrogate-model-assisted method to construct a cable forces predictor ahead of the structural optimization process, so that cable forces can be effectively predicted rather than optimized in each iterative round. Additionally, B-spline interpolation curve is adopted for variable condensation when sampling for the surrogate model. Finally, the structure optimization in the second sub-problem is performed by leveraging an optimization program based on particle swarm optimization method. The performance of the proposed framework is tested with a practical engineering application. Results show that the proposed method showcases good efficiency and accuracy. The theoretical raw material consumption of the towers and the cables is 32% lower than the original design.