Abstract: According to the seismic reliability characteristics of series isolated building structure systems, the calculation formula for the seismic reliability of series isolated structural systems is derived. In addition, based on the probabilistic seismic demand models of the superstructure, the isolation layer and the substructure of isolated structure, the calculation method of the seismic vulnerability of series isolated structures is put forward. Finally, taking a typical high-rise frame-core wall base-isolated structure as an example, a finite element model of the high-rise isolated structure is built and used to conduct seismic dynamic response analysis. The seismic damage probability of the isolated structure is analyzed by the proposed method, and the seismic vulnerability curves of the high-rise isolated structure are obtained in the state of severe damage. The results show that the failure of the isolation layer is the key factor that affects the integral seismic reliability of high-rise isolated structural systems.