Abstract: As a generalized structural form of base-isolated buildings, inter-story isolated buildings have received more and more attention. In modal coordinates, the nonlinear equation of motion of the inter-story isolated building is established firstly. Based on the equivalent linearization and complex mode superposition method, the response spectrum analysis method for predicting the seismic response of the inter-story isolated tall building is presented. Taking an inter-story isolated building with height of 125 m as an example and selecting the recorded seismic waves matching the code response spectrum from the PEER databased, the floor seismic responses calculated by the nonlinear time domain analysis and the equivalent linearization method are compared. The contributions of higher modes to structural response are analyzed. The response error caused by the real mode method (forced decoupling approach) is quantified. Furthermore, the effectiveness of the complex modal response spectrum method for the structural seismic response analysis is evaluated. The results show that the forced decoupling approach underestimates the top acceleration of lower structure by about 35%, and the CCQC method provides a good prediction on displacement and shear force. This study provides a theoretical basis for the standardized calculation of seismic response of the inter-story isolated tall building.