Based on the uncertain problem during the design of the fatigue life of drive axle housing assemble, entity model of drive axle housing assemble of some commercial vehicle is built by UG. According to national standard of the Bench Test, with finite element method, the finite element model is built and the static strength analysis is made by the FEM-software ABAQUS 6.8. On the base of the result of stress-strain analysis and the model validation, with the fatigue software FEMFAT 4.7D, the research on the cumulative damage and endurance limit safety factors is studied in terms of the Miner modified fatigue theory in the drive axle housing assemble. The results show that the model and method is reasonable and effective. It is helpful to optimize the structure parameter in the drive axle design through the optimization algorithm in the automobile.