Under the action of earthquakes, the dynamic responses of cross-sea bridges are greatly influenced by the dynamic interaction between each pier and the surrounding water. Based on Morison equation, this paper mainly explores the responses of a continuous girder cross-sea bridge in uncontrolled and semi-active control modes, under the combined effect of earthquake and hydrodynamic pressure. First, a simplified two-degree-of-freedom (2DOF) analysis model was constructed for the bridge: the combined stiffness was proposed to reflect the effects of the bending and shear deformation features of the pier; the pier mass was aggregated on the top of the pier as the additional pier mass, using the shape function of linear deformation; the hydrodynamic pressure distributed on the pier was calculated by the Morison equation, converted into the equivalent node load on the top of the pier, and further transformed into the additional hydrodynamic mass. Then, a magnetorheological (MR) damper was added between the pier and the girder. The semi-active algorithm of the MR damper was designed based on the clipped-optimal control algorithm. The control force of the MR damper was optimized by the H2/LQG active control method. The results show that the hydrodynamic pressure changes the dynamic features of the bridge and increases the seismic responses of the bridge, calling for a stronger control force for semi-active control; the impact of hydrodynamic pressure must be considered in the seismic design of cross-sea bridges; the MR semi-active control can effectively suppress the dynamic responses of cross-sea bridges, enhancing the seismic safety of the bridge. The research results provide new insights into the vibration control of cross-sea bridges.