In the present work, the biogas production potential of star-fish waste was estimated using response surface methodology (RSM). After grinding and centrifugation of star-fish waste, only the supernatant was used as a substrate. The supernatant contained 55% of total COD in the whole feedstock. Sixteen experimental sets for biochemical methane potential (BMP) test were made according to central composite design at various inoculum/substrate (I/S) ratios, substrate concentrations (2.0~8.0g COD/L), and buffer capacities (0-5g NaHCO3/L). Methane yield (MY) increased as 1/S ratio increased and substrate concentration decreased. By applying regression analysis, MY was well fitted based on the actual value to a second order polynomial equation (p=0.0110): Y = 251.81 + 54.59X1 - 8.46X2 + 13.09X3+ 2.29X1X2 - 7.25X1X3 + 4.90X2X3 - 8.24X1(2) - 1.10X2(2) - 4.38X3(2), where X1, X2, X3, and Y are I/S ratio, substrate concentration, buffer capacity, and MY, respectively. The highest MY of star-fish was estimated to be 334 mL CH4/g COD, accounting for 52% of energy content in the feedstock.