Abstract: The strait seabed is usually a deep sediment basin with various types of micro-topographies, and its seismic responses are strongly affected by the micro-topographies. A nonlinear seismic response analysis of 2D refined finite element simulated model for a strait section crossing Qiongzhou Strait is established. In the response analyses of the cross-strait site, the basin structure, surface micro-topography and spatial inhomogeneous soil with variable S- and P- wave velocities are considered. Considering the regional tectonic setting and historical seismicity around the strait site, three bedrock recordings of moderate-far field earthquake scenarios are justified for determining the bedrock shakings. The combined influences of seabed cross-section topography and spatial inhomogeneity of soils on the seismic site responses are complicated and significant, including the basin resonance-like effects and the aggravating effect of the local concave seabed surface edges and seabed convex areas on soil amplification. The simulated results imply that it is easier to propagate upward earthquake waves through the soil deposits for the bedrock motion components close to the fundamental frequency of strait seabed. Compared with the horizontal seabed site responses, the influences of the surface micro-topography on the vertical seismic responses are more significant. The generated surface waves at seabed surface due to the wave constructive interference of the horizontal and vertical components upward earthquake waves aggravate the horizontal responses of seabed site surface.