To investigate the dynamic responses of the train-track-bridge system and running safety under tornadoes, the Kou-wen 3D model is used to simulate the tornado wind field, firstly. The time history of wind loads on vehicles and bridges under the action of moving tornadoes is determined based on quasi-definite theory. Then, the dynamic equations of the vehicle subsystem and track-bridge subsystem are established by using the multibody dynamics approaches and finite element method, respectively. The dynamic equations of the wind-train-track-bridge system are established based on the wheel/rail nonlinear contact relationship, and the dynamic response of the system is solved by the separation iteration method. In the numerical calculations, a road-cum-rail cable-stayed bridge was taken for a case study. The aerodynamic coefficients of bridge and train are determined by wind tunnel test and CFD numerical simulation. The influence of the direction of tornado movement, tornado intensities and running speeds on train-bridge system dynamic response and train running safety is analyzed. The results show that the vertical dynamic response of the bridge is more significant than that of the horizontal, and the vertical wind speed plays a critical role in the vertical displacement of the bridge. When the vehicle passes through the maximum position of wind load, both the lateral and vertical vibration response of the vehicle reaches its maximum value, and the vehicle dynamic response is affected by both tornado load and bridge dynamic response. The maximal running velocity under the EF1 and EF1.3 tornadoes is 180 km/h and 114 km/h, respectively.