The design optimization of vehicle body structure is addressed to reduce interior noise and improve customer satisfaction in this paper. The structural-acoustic model is developed by using finite element method. The frequency response of structural-acoustic system is computed by modal analysis method. The optimization problem is constructed to minimize the sound pressure level in the right ear of the driver. The sensitivity analysis is carried out to find the key panels to be optimized as design variables and improve the efficiency of optimization computation. Response Surface Method (RSM) is utilized to develop the surrogate model and optimize the vehicle Noise Vehicle and Harshness (NVH) behavior. A 9dB reduction of sound pressure level (SPL) in the right era of the driver is obtained through geometric optimization for panels. Furthermore, the topology optimization model is developed to search the optimal layout of constrained layer damping treatments in the front floor. The evolutionary structural optimization (ESO) method is used to solve the topology optimization problem. The results show that a combination of geometric optimization for panels and topology optimization for the layout of constrained damping treatments will give rise to a 15 dB reduction of sound pressure level in interior noise of vehicle. The proposed method provides an effective design tool and demonstrates potential applications in a real vehicle to obtain a lightweight vehicle body and improve NVH behavior.