An optimization method for the strength and stiffness matching of a driven axle under asymmetrical loading was proposed to solve the problem of early stage failures in a heavy vehicle. The influence of stiffness of the driven axle on the load distribution was analyzed. On these bases, the optimization on the structure was carried out with the structural strength and fatigue life as constraints and the balanced strain of the splines as an objective. The results of FEA (finite element analysis) on the modified driven axle indicate that the stress at the critical part is significantly reduced by 90.3 MPa. Additionally, the torque distribution of the driven axle is more reasonable and the service life is improved by 72.2%.