To release sugars effectively from sweet sorghum bagasse (SSB), a cellulose solvent and organic solvent-based lignocellulose fractionation pretreatment approach was studied using response surface methodology (RSM). Based on RSM's central composite design, a batch experimental matrix was set up to determine the effects of reaction time (20-60 min) and temperature (40-60 degrees C) on delignification, total reducing sugar yield, glucan digestibility, and overall glucose yields following a pretreatment-hydrolysis process. The optimum pretreatment conditions of 50 degrees C and 40 min led to 51.4% delignification, 86% overall glucose yield, and 61% overall xylose yield. An effort has also been made to obtain predictive models to illustrate the correlation between independent and dependent variables using RSM. The significance of the correlations and adequacy of these models were statistically tested for the selected objective functions. The optimum pretreatment condition predicted by the model was 49.1 degrees C and 39.2 min which matched the experimental data well. Results from this study can be applied to large scale biorefineries using sugars released from SSB for producing various biofuels. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:367-375, 2014