This study systematically investigated the anaerobic digestibility of durian shell and focused on maximizing the methane yield using response surface methodology. Results showed in the feedstock to inoculum (F/I) ratio range of 0.2-2, a lower value was preferred. Meanwhile the methane yield showed a sharp rise first followed by a decline as the organic loading (OL) increased from 3 to 27g VS/L. The highest experimental methane yield (EMY) was calculated to be 170.6ml/g VS at F/I ratio of 0.2 and organic loading of 20.45g VS/L. To make the combination of F/I ratio and OL more practical, 0.5 was set as the optimum F/I ratio, when the highest EMY was obtained to be 165.0ml/g VS at the OL of 20.45g VS/L. Characteristics of final effluent implied the anaerobic system was stable. This study is important to promote the application of durian shell into anaerobic digestion from theory to practice.