The frontal crash optimization of an engine room member using the response surface method was studied. The engine room member is composed of the front side member and the sub-frame. The thicknesses of the panels on the front side member and the sub-frame were selected as the design variables. The purpose of the optimization was to reduce the weight of the structure, under the constraint that the objective quantity of crash energy is absorbed. The response surface method was used to approximate the crash behavior in mathematical form for optimization procedure. To research the effect of the regression method, two different methodologies were used in constructing the response surface model, the least square method and the moving least square method. The optimum with the two methods was verified by the simulation result. The precision of the surrogate model affected the optimal design. The moving least square method showed better approximation than the least square method. In addition to the deterministic optimization, the reliability-based design optimization using the response surface method was executed to examine the effect of uncertainties in design variables. The requirement for reliability made the optimal structure be heavier than the result of the deterministic optimization. Compared with the deterministic optimum, the optimal design using the reliability-based design optimization showed higher crash energy absorption and little probability of failure in achieving the objective.