The wind noise becomes the foremost noise source when the vehicle runs at high speeds. The high frequency characteristics of the wind noise source and the effective performance of seal rubbers for insulating the leakage noise make the research on the transmission loss (TL) of the automotive door sealing system significant. To improve the TL of the automotive door sealing system could effectively decrease the interior wind noise of vehicles at highway speeds. In this study, firstly two steps of simulation on the TL of automotive door sealing system are carried out. Through the finite element (FE) tool the compression simulation of the door seal rubbers is performed and the compressed geometry of seal rubbers can be obtained. Then with the final compressed geometry and the pre-stress modal results of the automotive door sealing system the TL of the whole door sealing system can be acquired by hybrid finite element – statistic energy analysis (FE-SEA) method. For the low Mach flow of ground vehicles, incompressible computational fluid dynamics (CFD) tool is used to simulate the fluctuating surface pressure on a sedan body before the Corcos’ model and the boundary element method (BEM) are used to obtain the wind noise source excitation. Then full vehicle SEA model is built to predict the interior sound pressure level and speech intelligibility inside the vehicle under the wind noise source excitation. The TL of the automotive door sealing system is considered into the full vehicle SEA model for optimization with orthogonal experiment optimization procedure on the TL of the automotive door sealing system based on the speech intelligibility. The automotive door seal rubber with good sound insulation is finally obtained.