This paper describes application of Design of Experiments (DOE) technique and optimization for mass reduction of a Sports utility vehicle (SUV) body in white (BIW). Thickness of the body panels is taken as design variable for the study. The BIW global torsion, bending and front end modes are key indicators of the stiffness and mass of the structure. By considering the global modes the structural strength of the vehicle also gets accounted, since the vehicle is subjected to bending and twisting moments during proving ground test. The DOE is setup in a virtual environment and the results for different configurations are obtained through simulations. The results obtained from the DOE exercise are used to check the sensitivity of the panels. The panels are selected for mass reduction based on the analysis of the results. This final configuration is further evaluated for determining the stiffness and strength of the BIW. Panel selection for the study is based on global modes, stiffness and strength requirements only. Panels critical to other and overlapping functional requirements are not considered for the study. Direct optimization is also carried out and results are compared with the final configuration based on DOE.