Abstract. In recently years, many sea-crossing bridges were built in some countries. For the complexity of seafloor condition and the stochastic characteristics of earthquakes, it is necessary to research the seismic responses of these sea-crossing bridges located on seawater layer and irregular bottom conditions. In this paper, a theory of the spatial varying ground motions was derived considering the wave propagation in soil and water. The effects of sea water layer, wave passage, coherence, local site and soil saturation on the seismic responses of a cable-stayed bridge were researched. The transfer function was used to calculate the local site effect and soil saturation effect. The seawater layer effect was studied via a simple medal from Crouse and Quilter. Multi-support and tri-direction excitations were utilized with large mass method. The seismic responses of a long span cable-stay bridge in the site conditions with and without seawater were compared. The results present that the seawater layer affects the earthquake response of bridge greatly, and the soil types have different effects on the different component of bridge. The research will help reasonably evaluate the security of sea-crossing bridge under earthquake excitation.