The fatigue life of a spherical hinge suspender connecting the locomotive structural frame and axle box is the key factor affecting the reliability of locomotive body. Firstly, the ABAQUS software is used to establish the finite element model of a spherical hinge suspender, and the fatigue life of the spherical hinge suspender is predicted. The result shows that the fatigue life of the spherical hinge suspender does not satisfy with the expected life. Then, the SolidWorks is used to establish a 3D model of spherical hinge suspender, and the HyperMesh is adopted to mesh the rubber parts. The variables of support reaction force and displacement are derived by using ABAQUS to calculate the radial stiffness of spherical hinge suspender. The geometric parameters of free surface of spherical hinge are selected as the design variables, and the structural optimization with the fatigue life as an objective function is carried out under the condition of radial stiffness restraint. Under the Isight environment, the multi-island genetic algorithm is used to obtain the reasonable free surface geometric parameters of spherical hinge. The result shows that the fatigue life of the optimized spherical hinge suspender satisfies the design requirements. Finally, the stiffness tests for the original and optimized structures are individually carried out in a radial loading mode, the results show that the calculated stiffness coefficient of the optimized structure is consistent with the test one, and the simulation life is well fit with that obtained from the fatigue life curve.