In order to study the optimization of structural design parameters of cable-stayed bridge, the main tower height, cable area and tower stiffness of the cable-stayed bridge are selected as the analysis parameters based on an engineering example of a cable-stayed bridge. Define local structural safety factor R and equivalent safety factor E . The maximum stress of the main tower, the displacement of the top of the main tower, the maximum stress of the stay cable, the bending moment at the base of the main tower, the maximum stress of the main beam and the maximum deflection of the main beam, which can reflect the internal force performance of the cable-stayed bridge, are selected as the objective functions. Firstly, parameter optimization analysis based on control variables method is used to obtain the optimal value of a single design parameter of cable-stayed bridge. Secondly, based on the orthogonal test method, the height of the main tower is 84.52m, the cable area is increased by 20%, and the original stiffness of the main tower are the best combination scheme. At the same time, the rank about influence degree of parameters is: the main tower height, the second is the cable area, and the last is the stiffness of the main tower. The main tower height and cable area should be considered in the design and parameter optimization of cable-stayed bridge.