In order to clarify the influence of hydrodynamic on dynamic response of bridge with complex piers submerged in reservoir, based on the continuous beam of a 4-column pile column frame pier in Xiaolangdi Reservoir of Yellow River, taking 4-column pile column frame pier and bridge as the object separately, the numerical analysis model of bridge (pier) - water interaction is established by ANSYS. The flow around deep-water piers is analyzed. For the single pier (SP) and the pier of the bridge (BP), the dynamic responses of different flow velocities, water depths and wave heights and the combined action are studied. The research shows that detouring flow analysis shows that velocity field and pressure field of each column are asymmetric. Specifically, for this bridge, due to the columns interfere with each other, the velocity difference of 1#, 4# column is more obvious than that of 2#, 3# column. Maximum and stability values of the dynamic response of SP and BP increase with the increase of flow velocity and depth. Specifically, as the water flow velocity increases, the maximum response of the dynamic response increases linearly, while the stable response of the dynamic response increases in the form of a quadratic curve. When the water depth does not exceed 50 m, the maximum and stable values of the dynamic response gradually increase in the form of a quadratic curve. When the wave acts alone, the dynamic response of SP and BP is the largest at the wave crest and the smallest at the wave trough. The maximum dynamic response at the wave crest and trough increases with the increase of wave height. With the increase of water depth, the dynamic effects of waves on SP and BP are more significant. Under the combined action of wave and current, the dynamic response of SP and BP increases with the increase of wave height and water depth. For different flow velocities, the maximum value of dynamic response at wave crest increases with the increase of flow velocity, and the maximum absolute value of dynamic response at wave trough decreases with the increase of flow velocity. Dynamic response under the combined action of wave and current is not the superposition of the dynamic response under the separate action of wave and current. The maximum value of dynamic response appears in wave crest and wave trough, indicating that the current does not change the action of wave field, and the wave still plays a leading role. Specifically, the influence of water on the dynamic response of BP is: pier bottom bending moment > pier bottom shear force > pier top displacement and the influence of water on the dynamic response of SP is: pier bottom bending moment > pier top displacement > pier bottom shear force.