Ground motion characteristics are relatively affected by the local conditions of the site, and the site often needs backfill and foundation treatment before construction. Therefore, it is necessary to study the influence of the backfilled layer on the seismic response of the site. In this paper, we analyzed the two-dimensional seismic response of a nuclear power site with the software MIDAS GTS NX, i.e., thickness, shear wave velocity, and density of controlled boreholes at the site. Time histories of input ground motion have a great impact on ground motion parameters, thus the results of these parameters can vary significantly. To maximize the response of the structure and narrow the gap between earthquake action on the structure and the actual earthquake action, five time-history samples were fitted as the input seismic ground motion, and three models with different shear wave velocities of backfilled soil layer were established. The results showed that, with constant thickness of backfilled soil and constant total thickness of the model, the horizontal peak acceleration of the surface decreases with increasing shear wave velocity of the backfilled soil, but the amplitude was gradually reduced. The surface horizontal peak acceleration will no longer be affected when the shear wave velocity reaches a certain value. We also found that with increasing shear wave velocity of backfilled soil, the spectral value of the entire response spectrum will generally decrease.