To realize the structural light weighting design of the transmission components of engineering vehicles on the basis of life in control, this paper took wheel loader as an example, collected the time-domain load signals of the transmission system in typical working conditions, provided processing steps for load spectrum synthesis by a certain percentage, and generated the program load spectrum which consisted of various amplitudes and means. The load spectrum can be used for fatigue loading at the output flange of gearbox. Then, the finite element model of the flange was established, and the stress analysis was carried out in the stress concentration location such as fillet. The prediction method of fatigue life on the base of program load spectrum was given. After the fatigue life prediction based on the compiled load spectrum and the theory of cumulative fatigue damage, the fatigue life of outside fillet of the flange, where is of maximum stress, is obtained. It was possible to obtain adequately fatigue prediction results in engineering vehicle design, using load spectrum, finite element analysis, and a stress-life approach to fatigue damage calculations.