Based on the 1–3 identical high-rise buildings with pile-raft foundation, a series of building-site two-dimensional finite element analysis models with different building spacings is established. Then, considering the nonlinear characteristics of soil and structure, the static-dynamic coupled numerical simulations are conducted to study the structure-soil-structure interaction (SSSI) under different ground motion. The results show that: 1) Adjacent high-rise buildings have the most unfavorable impact on the peak acceleration of the 1/4–1/2 height floors of the middle building, and increase the normalized response acceleration spectra value of acceleration near the second natural period of the structure; 2) Adjacent high-rise buildings have the most significant impact on the inter-story drift of the top, bottom and basement of the middle building; 3) Adjacent high-rise buildings redistribute the total horizontal shear force of the pile top of the middle building among the pile foundations, so that the peak value of the pile top shear force of each pile changes significantly, which is extremely unfavorable to the seismic safety of the structure. It should be taken seriously in the seismic design of structures. In addition, the structure spacing that results in favorable or unfavorable effects is discussed, and the reasons for the impact are analyzed.