Abstract: Due to the diversity of structural seismic design, it often leads to the deviation of equipment placements from the structural centroid. From the historical earthquakes, the damage degree of equipment with various usage functions in buildings is often higher than that of the main structure. Moreover, the velocity pulse and torsional component of ground motions have significant influences on the structure. Therefore, this paper focuses on these two key influencing factors and conducts seismic response analysis on equipment-structure coupling systems with different equipment eccentricities. Firstly, this study obtains the rotational component of ground motion based on the frequency domain method and verifies the feasibility of the modeling method based on the scaled shaking table test. On this basis, by changing the position of the equipment on the top floor of the main structure, three equipment-structure coupling systems with top floor eccentricities of 0%, 2%, and 4% are designed, and be adopted to simulate the seismic performance. The results show that the seismic response of the main structure will increase under the influence of both the velocity pulse and the torsional component of ground motions. Moreover, when both factors are considered, the growth rate of the main structure’s maximum acceleration can reach to 109.57% and 101.16% under the DBE and MCE level. Due to the rotational inertia generated by the eccentric placement of equipment being opposite to the effect of the torsional components on the structure, the equipment eccentricity has different influences on the seismic performance of the main structure and the equipment. As the equipment eccentricity increases, the growth of the acceleration of the main structure and the equipment decrease (52.4%→43.2%、52.6%→44.2%) and increase (3.2%→38.5%、2.7%→33.5%) under the DBE and MCE level., respectively. Therefore, in the seismic design of structures, the influences of the above factors on the main structure and the attached equipment should be separately considered.