The extraction processing of lycopene from watermelon was investigated in this paper. Based on single factor experiments, response surface methodology (RSM) was adopted to study the key parameters such as number of extraction, extraction temperature, extraction time in order to increase extraction rate of lycopene. A second order quadratic equation was established and the applicability of model and interaction involved factors on predicting the lycopene extracting content was verified. The results indicated that the optimum extraction conditions were hexane (containing 2% dichloromethane) as extraction solvent, ratio of solvent to raw material of 3:1 (mL/g), number of extraction of 2, extraction time of 1.9 h and extraction temperature of 29.8°C. Under these conditions the extracting content of lycopene was 14.71±0.22 mg/kg, which is well in agreement with value predicted by the model.