In order to study the vortex-induced vibration characteristics of the Π-shaped girder section and predict its response, taking a long-span steel-concrete Π-shaped girder cable-stayed bridge as the background, the vortex-induced vibration characteristics of the girder with different mass and damping ratios were tested in the wind tunnel. The dynamic parameters of the girder were identified by free vibration test, and the amplitude-varying damping ratio and amplitude-varying frequency of the girder under different wind speeds were extracted. Furthermore, the vortex-induced force model of the main beam is established based on the amplitude-varying aerodynamic derivative. At the same time, the vortex-induced force model is used to predict the vortex-induced vibration amplitude and vortex-induced vibration interval of the main beam under different damping ratios. The results show that the vertical modal parameters of the steel-concrete Π-shaped girder show different development rules in different wind speed ranges, which can be divided into five wind speed ranges. Based on the Scanlan self-excited force model, a vortex-induced force model containing only two aerodynamic derivatives of H1 and H4 is established. By comparing with the results of vortex-induced vibration amplitude and vortex-induced vibration interval of wind tunnel test, the correctness of the vortex-induced force model and its vortex-induced aerodynamic derivative method is verified. At the same time, compared with the wind tunnel test results under different damping ratios, it is verified that the vortex-induced force model is universal. The research conclusions can provide reference for the establishment of vortex vibration mechanism and vortex excitation force model of Π-shaped main girder section.