The traditional fatigue life prediction methods based on the S-N curve all believe that the parameters in the model are deterministic constants and can be categorized to the deterministic life prediction. However, in practice, it is difficult to carry out a large number of experiments due to the limitation of time or the possible shortage of funds. In addition, the specimens used in the experiments are not exactly the same, and the test operations and data reading depend on the accuracy of the test equipment as well as the subjective judgment of the testers, which result to the uncertainty of the S-N curve. Therefore, the uncertainty should be considered in order to improve the accuracy of the fatigue life prediction. In this paper, the uncertain factors affecting the fatigue life of welded joints are summarized, and the generalized polynomial chaos (gPC) is introduced into fatigue life prediction. A novel probabilistic fatigue life prediction method combined with the nonlinear cumulative damage model considering the uncertainty of the S-N curve is constructed. An illustrative example is presented to demonstrate the advantages of the proposed approach.