The FRF-based substructuring method is one of the most powerful methods in analyzing the responses of complex built-up structures with high modal density. In this paper, a general procedure for the design sensitivity analysis of a vibro-acoustic system has been presented using the FRF-based substructuring formulation. For an acoustic response function, the proposed method gives a parametric design sensitivity expression in terms of the partial derivatives of the connection element properties and the transfer functions of the substructures. The derived noise sensitivity formula is combined with a non-linear programming module to obtain the optimal design for the engine mount system of a passenger car. The objective function is de"ned as the area of the interior noise graph integrated over a concerned r.p.m. range. The interior noise variations with respect to the dynamic characteristics of the engine mounts and bushings have been calculated using the proposed sensitivity formulation and transferred to a non-linear optimization software. To obtain the FRFs, a "nite element analysis was used for the engine mount structures and experimental techniques were used for the trimmed body including the cabin cavity. The optimization based on the sensitivity analysis gives the ideal sti!ness of the engine mount and bushings. The resultant interior noise in the passenger car shows that the proposed method is e$cient and accurate.