To accurately predict the fatigue life of vehicle frame, MBS and FEM were integrated. A full multi-body dynamic model was established first, according to the spectrum of road surface which simulate the china’s pavement condition, loading history at 11 critical positions was calculated. Then the stresses influence coefficient was calculated in finite element model which establish in ANSYS. At the same time, according to the frame material’s S-N curve and character of the frame, the frame’s S-N curve was received. Finally, based quasi-static stress analysis, the frame structure’s fatigue life was predicted by using MSC-FATIGUE. The fatigue analysis results were reasonable and could be the foundation for the research about lightening the structure of the frame.