Self-piercing riveting (SPR) has been widely used in automobile industry, and the strength prediction of SPR joints always attracts the attention of researchers. In this work, a prediction method of the cross-tension strength of SPR joints was proposed on the basis of finite element (FE) simulation and extreme gradient boosting decision tree (XGBoost) algorithm. An FE model of SPR process was established to simulate the plastic deformations of rivet and substrate materials and verified in terms of cross-sectional dimensions of SPR joints. The residual mechanical field from SPR process simulation was imported into a 2D FE model for the cross-tension testing simulation of SPR joints, and cross-tension strengths from FE simulation show a good consistence with the experiment result. Based on the verified FE model, the mechanical properties and thickness of substrate materials were varied and then used for FE simulation to obtain cross-tension strengths of a number of SPR joints, which were used to train the regression model based on the XGBoost algorithm in order to achieve prediction for cross-tension strength of SPR joints. Results show that the cross-tension strengths of SPR steel/aluminum joints could be successfully predicted by the XGBoost regression model with a respective error less than 7.6% compared to experimental values.