The paper aims to analyze the stress–strain response of building steel under low-cycle multiaxial fatigue and to accurately evaluate the fatigue life of specimens by selecting the more important relevant factors that affect fatigue behavior. Based on this, low-cycle multiaxial fatigue experiments of Q355D notched specimens under different multiaxial loading are carried out. Firstly, the fatigue behavior of notched specimens under different loadings and the relationship between the biaxial strain amplitude ratio and fatigue life are analyzed. Secondly, Grey correlation analysis, Pearson correlation analysis, and Random Forest importance analysis are used to screen out the important factors affecting fatigue life. Finally, the grey MGM (1, N) model is used to predict the fatigue life of notched specimens, and the results show that the predicted life based on Random Forest importance analysis is in good agreement with the experimental life. In this paper, the multiaxial fatigue problem is decoupled into two sub-problems, i.e. screening out related factors and life prediction based on the related factors, which can be used as a reference for life prediction in structural design.