Abstract: The seismic response of nuclear power plant is impacted by soilstructure interaction (SSI). In this paper, response of the 10 MW High Temperature Gas-cooled Reactor (HTR-10) under three-directional seismic excitation was analyzed considering SSI effect. The coupled finite element model of soil-structure was established, and the seismic wave propagation in infinite field was simulated by constructing the artificial boundary condition. Accuracy of the model was verified. The seismic response of HTR-10 building was calculated utilizing this model, and the response spectra of different floor levels were analyzed. In horizontal direction, the response spectrum shapes of each floor are similar, and the influences of SSI are basically the same. In vertical direction, the responses are significantly relevant to the vertical frequency characteristic of each floor, and responses of each floor are in large difference. In general, SSI inhibits the vertical response, and this effect becomes more remarkable as the floor increases. When the frequency of floor is close to that of the soil, responses of this floor have an obvious amplification compared with other floors.