The alcohol- based fuels have attracted the attention of alternative fuel researchers. Fusel oil is an alcohol- based fuel collected as a by-product during bioethanol production. The main objective of this study is to determine the optimal blending ratio of fusel oil- diesel regarding the performance and emissions of spark ignition engine using response surface methodology based on CCD design. In this research, experimental investigations have been performed with different fusel oil- diesel blends (0%, 5%, 10%, 15% and 20%), different loads (0%, 25%, 50%, 75% and 100%) and different engine speeds (1400, 1700, 2000, 2300 and 2600 rpm). The multi-objective optimization was performed to maximize the power and torque, and minimize BSFC, NOx, UHC and CO emissions. The best combination of engine parameters was found to be 11.57% fusel oil, 40% load and 2264 rpm engine speed. The optimal values were 1.9 kW, 10.9 N.m, 354.5 g/kWh, 0.19, 54.5, 2.34 and 87.7 (V%) for power, torque, BSFC, CO, UHC, CO2 and NOx emissions, respectively. The results showed that fusel oil usage increased power and torque. It was also found that both NOx and UHC emissions decreased.