This paper is mainly focused on the dynamical response and the structural fatigue situation of a manual gear-box case,which is based on the stiffness coupling with the effect of the gears. First of all,the FEM model was established and the accurate model was acquired by comparing the simulation results with the experiment results. Then,we established the coupling analysis model of structure dynamics considering on parts of gears,shafts as well as the structural flexible case,using the Romax software. The working processes under different gears were simulated accurately by the model and the bearing loads of the gearbox were obtained. Then we loaded the frequency bearing load on the FEM model and obtained the stress response of the danger area. Finally,the vibration fatigue life on the danger area of the gear-box case was calculated and analyzed by the sample assessment method.