To determine the main factors affecting the structural response of a steel-concrete composite beam cable-stayed bridge and its degree of influence, the parameter sensitivity analysis was carried out based on a steel-hybrid composite beam cable-stayed bridge under construction. MIDAS/Civil was used to establish a finite element simulation model, and uniform design experiments, multivariate linear regression analysis, and statistical test methods were introduced from experimental design and statistics perspectives. Taking the linear shape of the main beam, the displacement of the main tower, and the cable force of the main beam under the bridge forming state as the structural target response, the elastic modulus of the main tower and the concrete beam of the main beam, the elastic modulus of the cable, the initial tension of the cable, the bulk density of the bridge deck, and the tension control stress of the steel bundle of the bridge deck were selected for sensitivity analysis. The results show that the initial tension of the cable, the bulk density of the bridge deck, and the cable-stayed elastic mold are sensitive parameters of the linear bridge shape and the deviation of the bridge tower, and the sensitivity of the initial tension of the cable is much greater than that of the other two parameters. The sensitive parameters of the bridge cable force are the initial tension of the cable and the bulk density of the bridge deck. The proposed method can accurately obtain the sensitivity parameters of the bridge's structural response in the bridging state.