An efficient and accurate hybrid reliability analysis method is proposed in this paper to quantify the risk of an axially loaded single pile considering pile-soil interaction behavior and uncertainties in various design variables. The proposed method intelligently integrates the concepts of the response surface method, the finite difference method, the first-order reliability method, and the iterative linear interpolation scheme. The load transfer method is incorporated into the finite difference method for the deterministic analysis of a single pile-soil system. The uncertainties associated with load conditions, material and section properties of a pile and soil properties are explicitly considered. The risk corresponding to both serviceability limit state and strength limit state of the pile and soil is estimated. Applicability, accuracy and efficiency of the proposed method in the safety assessment of a realistic pile-soil system subjected to axial loads are verified by comparing it with the results of the Monte Carlo simulation technique.