Based on the single factor experiment, Box-Behnken central composite design of response surface methodology was applied to optimize conditions of the ethanol fermentation of sweet sorghum juice. Taking the production of ethanol as the evaluation index, this method investigated the main factors, such as fermentation temperature, pH, and inoculum, to the influence of fermentation. The experimental data indicated that the application of the model equation for evaluating the optimum response values was verified effectively. The optimum fermentation parameters for the sweet sorghum juice converting to ethanol were obtained as: temperature 27.7 degrees C, pH value 5.4, inoculation 5%, and the production of ethanol 9.3%.