Supercritical fluid extraction with supercritical CO2 (SC-CO2) is applied to extract the vegetable oil from watermelon seeds. A small face central composite design (SFCCD) is employed to optimize the extraction parameters. The maximum value of cumulative extraction yield (CEY) for watermelon oil is found to be about 51.83 wa, and was obtained when SC-CO2 extraction is carried out at 60 degrees C, 400 bar, 15 g/min solvent flow with 10% co-solvent and with 0.50 mm particle diameter. The analysis of response surface showed that, extracted data are adequately fitted to reduced second-order polynomial model and all independent variables, quadratics of independent variables and some interaction parameters between independent variables have significant effects on CEY. The correlation coefficients "R-square", "adjusted R-square" and "predicted R-square" values for reduced quadratic model are 0.9974, 0.9907 and 0.9226, respectively. The chemical composition of seed oil shows that 75.1% unsaturated and 24.9% saturated fatty acids are present in the seed oil. Further, it is found that watermelon seed is a high source of linoleic acid. (C) 2014 Elsevier B.V. All rights reserved.