NVH quality is one of the most important criteria by which people judge the design of a vehicle. The Powertrain Mounting System (PMS), which can reduce the vibration from engine to vehicle cab as well as the inside noise, has attained significant attention. Much research has been done on the isolation method for three- and four-point mounting. But the six-point mounting system, which is usually equipped in commercial vehicle, is seldom studied and should be paid more attention.In this paper, the support rod installed on the upside of the transmission case is considered as a flexible body. Thus a rigid-flexible coupling model of PMS is established and the necessity of the established model is analyzed by comparing the simulation results of the new model and those of the conventional model. Based on the traditional theory of energy decoupling and reasonable allocation of the natural frequencies, Adams and MATLAB are integrated into the optimization software iSIGHT to optimize the six-point PMS. The orthogonal experiment is used to determine the main factors that affect the optimization objective and the initial design parameters for further optimization. The Mixed Integer Sequential Quadratic Programming (MISQP) is used to obtain an optimal model of PMS. Finally the dynamic frequency response method is used to validate the optimal model.