Abstract: The increase dynamic analysis (IDA) curves of seismic responses of the underground large-scale frame structure (ULSFS) are investigated during the single horizontal earthquakes and horizontal-vertical earthquakes, respectively. The influence mechanism of vertical earthquakes on the seismic responses of different vulnerable positions is revealed. Aiming at the interlayer drift deformation and flexural deformation in the ULSFS, the interlayer drift ratio (IDR) and interlayer rotation angle (IRA) are employed as the seismic performance evaluation indexes. Therefore, the influence mechanism of vertical earthquakes on structural seismic performance is further revealed. The seismic fragility curves of the ULSFS are achieved during horizontal earthquakes and horizontal-vertical earthquakes, respectively. The results show that the vertical earthquakes have small seismic influences on the seismic fragility of the ULSFS based on the IDR. However, the vertical earthquakes enlarge the local flexural deformation of the ULSFS and decrease the seismic performance of the ULSFS based on the IRA. The seismic fragility considerably increases after considering the vertical seismic effects. The IDR aiming at the horizontal drift deformation and the IRA aiming at the interlayer flexural deformation are advised to be employed to assess the seismic fragility of large underground structures during both horizontal and vertical earthquakes comprehensively.