Soil-structure interaction has important influence on the seismic response of the structure. The rotation of isolation layer caused by vertical deformation of isolation bearing can increase the swing of upper structure, and then the seismic response of structure is enlarged. The calculation model involving SSI effect and rotation of isolation layer is developed based on Timoshenko theory. The equations of motion are formulated. Pseudo excitation method is used in seismic random response calculating. The influences of the rotation stiffness and soil parameters on the seismic response of isolated structures are discussed. Further analysis indicates that SSI affected the isolation effectiveness and the amplification factor on angular displacement of isolated structure is related to the ratio of soil-structure stiffness. The influence of isolation layer rotation stiffness on top acceleration and base overturning moment are not distinct. The vibration of isolation layer rotation stiffness has a great influence on the rotation angle of upper structure. When the rotational stiffness of isolation layer is relatively small, the angular displacement of upper structure is even larger than that of seismic structure.