An efficient and accurate algorithm is proposed to evaluate the reliability of cable-stayed bridges accounting for soil-pile interaction. The proposed algorithm integrates the finite-element method and the response surface method. The finite-element method is used to model the cable-stayed bridge including soil-pile interaction. The reliability index is evaluated based on the response surface method. Uncertainties in the superstructure, the substructure and load parameters are incorporated in the proposed algorithm. A long span steel cable-stayed bridge with a main span length of 1088 m built in China is considered as an illustrative example. The reliability of the bridge is evaluated for the strength and serviceability performance functions. Results of the study show that when strength limit states for both girder and tower are considered, soil-pile interaction has significant effects on the reliability of steel cable-stayed bridges. Further, a detailed sensitivity study shows that the modulus of subgrade reaction is the most important soil-pile interaction-related parameter influencing the reliability of steel cable-stayed bridges.