In order to more accurately simulate the vibration generated by vehicles crossing the bridge, the influence of the elastic action of the bridge support should be considered. Combining the separation method and the principle of vehicle dynamics, the calculation models of the vehicle, bridge and support were respectively established, and the vehicle-bridge-support coupling was carried out through the displacement coordination relationship and the force balance relationship. Based on the APDL language in ANSYS, taking a 30m simply supported box girder bridge as an example, the effects of bridge deck irregularity, support stiffness and damping on vehicle-bridge-support coupling dynamic response were studied and analyzed. The results show that the worse the flatness of the bridge deck, the greater the impact force on the bridge during the driving process of the vehicle, and the more severe the dynamic response of the bridge. Appropriately increasing the support stiffness can effectively reduce the dynamic deflection of the bridge and weaken the vibration response. The support damping has the effect of energy dissipation, and increasing the support damping has a significant effect on weakening the acceleration response of the bridge. When designing the bridge support, the stiffness and damping of the support should be appropriately increased to weaken the impact of the vehicle-bridge-support coupling vibration on the bridge.