ABSTRACT Based on the results of the shaking table model tests, the three-dimensional (3D) numerical simulation and analysis of the shaking table model test of the soil-box foundation-12-story reinforced concrete (RC) frame structure system are carried out using ABAQUS software in this paper. The material nonlinearity, geometric nonlinearity, and nonlinearity of the contact interfaces between the foundation and surrounding soil are considered in the numerical models. By comparing the simulated data with the measured data of the shaking table model tests, the simulated results are well consistent with the shaking table test records. It can be verified that the numerical models are reasonable. The numerical models’ key parameters are adjusted, and the influence of these parameters on the dynamic soil-structure interaction (DSSI) is analyzed. The results show that their influence is significant for studying the seismic response of the DSSI system, as the foundation buried depth decreases, the peak contact pressure and the peak inter-story drift at the top of the structure increase 30.69% and 45.24%, respectively, whereas the peak acceleration magnification factors at the top of the structure decreases 32.66%.