Testing engine performance using an engine dynamometer requires high technical researchers and many facilities. Nowadays, different variables of CAE program are used for identifying the engine performance instead of engine dynamometer test. This is more convenience, as it does not necessitate an abundance of engine dynamometer experiments and, in addition, produces better results. However, CAE programs also contain various variables which can affect engine performance. Those are coupled with each other, thus making it difficult to determine the effectiveness of different variables on engines. DoE (Design of Experiments) methodology is an efficient way to verify the magnitude of effectiveness on engine performance as well as making responses to be optimized at once without trial & error. This study used data from WAVE simulations, which modeled the DOHC SI engine with in-line 4 cylinders at 1500, 3000 and 4500rpm. DoE methodology is designed properly to determine the effectiveness of five variables on power, BSFC, and volumetric efficiency, as well as to find the optimal response conditions at each rpm through a minimized number of experiments. After finishing DoE process, all the results are examined concerning the reliability of test through a verification experiment.