Vehicle interior noise is an important factor affecting ride comfort. To reduce the noise inside the vehicle at the vehicle body design stage, a finite element model of the vehicle body must be established. While taking the first-order global modal of the body-in-white, the maximum sound pressure level of the target point in the vehicle, the body mass, and the side impact conditions into account, the thickness of the body panel as determined via sensitivity analysis is treated as the input variable, and the sample is determined by following the Hamersley experimental design. Specifically, the Elman neural network predicts the noise value in the vehicle, and a vehicle body structure optimization method that comprehensively considers NVH performance and side impact safety is established. The prediction errors of the Elman neural network algorithm were within 3%, which meets the prediction accuracy requirements. To achieve satisfactory restraint performance, the maximum sound pressure level of the target point in the vehicle is reduced by 5.92 dB, and the maximum intrusions of the two points on the B-pillar inner panel are reduced by 31.1 mm and 33.71 mm, respectively. The side impact performance is improved while the noise inside the vehicle is reduced. This study provides a reference method for multidisciplinary research aiming to optimize the design of vehicle body structures.