In order to reasonably match the variable stiffness and location of the Powertrain Mounting System (PMS) and optimize the ride comfort of commercial vehicle, a thirteen degrees of freedom (DOF) model of a commercial vehicle was established in Adams/view. Specially, the support rod installed on the upside of the transmission case was modeled as a flexible body.The vibration isolation provided by the PMS was evaluated in three aspects: the energy decoupling of the powertrain, the response force of the mount and the displacement of the powertrain. The energy decoupling ratio, the force RMS of the mount when force excitation was applied on the powertrain and the displacement of the powertrain Center of Gravity (C.G) when displacement excitation was applied on the vehicle chassis were selected as the optimal target. Adams and MATLAB were integrated into the optimization software iSIGHT to optimize the PMS. NSGA-II is used to obtain some Pareto-optimal solutions of PMS. Finally, a “performance function” is introduced to get the result of optimization.