Current knowledge on seismic analysis of underground structures is limited to analytical solutions, numerical methods and scaled model tests. Virtual hybrid simulation (VHS) is an efficient and economical analysis method that combines numerical approaches and experiment methods while taking the advantages of both. In this study, a VHS method employing a multi-axial experimental setup for seismic analysis of soil-structure systems is proposed and the corresponding VHS framework was developed using OpenFresco and OpenSees. To demonstrate the ability of the VHS method in accurately and efficiently capturing seismic behavior of underground structures, the proposed VHS method was applied to evaluate seismic response of the Daikai subway station, during which a good agreement was achieved when comparing the VHS results with those of the complete numerical simulation (CNS). Moreover, the advantages of the expanded multi-axial experimental setup in the proposed VHS method over the simplified single-DOF experimental setup are evaluated and discussed.