The residual stress field of aluminum alloy sub-frame was obtained through its casting process simulation by the software ProCast. Then, the residual stresses were loaded into the finite element model of aluminum alloy sub-frame for the mechanical analysis through the intermediate files as the initial condition. The fatigue life of the sub-frame was analyzed by using HyperMesh,ABAQUS,Fe-Safe and so on.The results showed that the residual stress decreased the working life in the longitudinal, lateral and vertical conditions by 48%, 71.3% and 32.5%, respectively.A bench test on the sub-frame was also performed. The results showed that the fatigue simulation results of residual stress were closer to the results of the bench test, and the performance index of the aluminum sub-frame satisfied the practical requirements.Therefore, the fatigue simulation considering the residual stress provides significance for the vacuum die casting aluminum alloy sub-frame production.