Realizable k-ε turbulence model has been used widely for engineering development. In this turbulence model, the default values of empirical coefficients such as C₂, σk and σε are obtained from some particular experiments. They are a good choice for most simulations-though may be not the best choice for simulating the aerodynamic characteristics of road vehicle. In order to improve the accuracy of simulation, a set of new empirical coefficients should be designed especially for simulating the aerodynamic characteristics of road vehicle. These empirical coefficients are found out by DoE (design of experiments) in this paper. Firstly the value range of empirical coefficients is decided by the laws that the aerodynamic force coefficients change with altering of empirical coefficients. Secondly 20 sets of empirical coefficients are obtained randomly by applying optimal Latin Hypercube method in Isight. After that the aerodynamic characteristics of MIRA model is simulated with these coefficients in Fluent. On that basis, Kriging model is used to establish approximation model. Regarding the results from wind tunnel experiments as the optimization objective, the empirical coefficients which are more suitable for simulating the aerodynamic characteristics of road vehicle are found out by applying Multi-island Genetic Algorithm. Finally, the new empirical coefficients are applied for the development of a real road vehicle, and its advantages are verified by the wind tunnel test. The results show that, by using the new empirical coefficients, the drag coefficient error is decreased by 2.5%, and the relative error of lift coefficient is reduced by 0.01 with faster convergence rate. However, the velocity contour around the rear of the MIRA model is not improved significantly compared with the velocity contour from PIV test.