A numerical solution for the dynamic responses of a train-bridge interaction system subjected to multi-support seismic loads was studied. The train vehicle was modeled by the rigid-body dynamics method, and the bridge was modeled by the finite element method. The vertical and lateral wheel-rail interaction forces were defined according to the wheel-rail corresponding assumption and the simplified Kalker creep theory. Three-dimensional seismic accelerations were incorporated using the large mass method. In a case study, the dynamic responses were simulated for a high-speed train traversing a steel truss cable-stayed bridge with different seismic intensities and different train speeds, and train safety was evaluated.