Heavy truck needs to use the vibration reduction technology to improve its quality. Nowadays, it is a useful and effective way for vibration reduction that by employing the proper Powertrain Mounting Systems (PMS) to reduce the vibration. One useful method to develop more effective mounting systems is through optimization techniques. Sequential Quadratic Programming (SQP) is an effective optimization technique. In this paper, design optimization of powertrain mounting system based on SQP method for vibration control is presented. The optimization objective is to find the highest decoupling ratio of the each mount while selecting the stiffness and orientations of individual mount. The constraints are imposed to keep the desired decoupled ratio in each orientation and the frequency corresponding to the decoupled ratio. A case study is given to validate the proposed method. The result shows that the value of optimized system, such as decoupling ratio, is improved significantly. Therefore, the method proposed in this paper is effective for the optimization of powertrain mounting system.