Abstract: In the seismic response analysis of large engineering structures, the soil-structure interaction can not be ignored. However, the calculation scale is usually very large due to the huge volume of the structure itself and the large scale soil model introduced after considering the soil-structure interaction. The low calculation efficiency has become the key factor restricting the performance analysis of such structures. A new soil-structure interaction analysis method is proposed, based on which an efficient seismic response analysis of large scale structures considering soil-structure interaction is realized. The decomposition method of element normal and shear relative displacement under different initial contact states is established. The contact behavior between soil and structure is described by using the three-dimensional zero thickness Goodman interface element. The inelastic deformation of the element is described by the interpolation method, and the control equation of the interface element with Inelasticity-separated method is derived. On this basis, a global calculation model considering soil-structure interaction and an efficient seismic response analysis method of large-scale engineering structures are established. Since the Woodbury formula is used to calculate the structural response in each iterative solution process, it is only necessary to iterate and update a small dimension local inelastic matrix. During the iteration process, the real-time updating and factorization of the large-scale global stiffness matrix required by the classical finite-element is avoided, which can greatly improve the efficiency of structural seismic response analysis. The effectiveness and efficiency of the proposed method is verified using numerical examples.