In the engineering background of a multistory frame structure, a PLAXIS 3D numerical model including superstructure, foundation and subsoil is built for elasto-plastic analysis. Firstly, in the PLAXIS 3D model, the same constraint condition is applied using SAP2000 to build the structural finite element model. The structural internal force in consideration of only gravity function from the two models is compared for verifying the calculation accuracy of PLAXIS 3D structure model. Secondly, the differences of structural internal force obtained by considering interaction or not are studied in two cases of small earthquake and large earthquake with pseudo-static analysis. Finally, the differences of foundation settlement between the full 3D model and the simplified model, in which superstructure is replaced by uniform distributed load, are analyzed. The numerical results indicate that full 3D model of superstructure, foundation and subsoil considers stiffness coordination directly and gives structural internal force and foundation settlement conforms to reality better than the simplified structure model.