Considering the correlation between different components, quantifying the failure probability of a high-level hyper-static structure under non-stationary seismic loading is of great significance in guiding earthquake-resistant design and fortification of bridges. In this study, a high-pier and large-span railway cable-stayed bridge in the mountainous region were employed to evaluate the seismic performance. First, the basic theoretical methods of the non-stationary random seismic motion simulation, equivalent extreme value theory based on extreme value distribution (EVD), improved Latin hypercube sampling (ICLHS) with unequal weighted fractional moment estimation and Pair Copula technique are presented. Second, the finite element analysis model of the cable-stayed bridge was established based on the OpenSees platform, the seismic response samples of the bridge were calculated under three levels of seismic ground motion to determine the first passage failure probability of the main components of the bridge under the design failure modes. Finally, the Pair Copula function was introduced to estimate the seismic system reliability of the cable-stayed bridge. The optimal Copula type that can describe the correlation between the bridge components was selected through goodness-of-fit tests such as AIC, BIC, and the minimum distance method. The failure probability of the entire system was obtained by calculating the selected Copula function type under seismic loading.