Bioethanol is considered the cleanest liquid fuel used as a substitute for depleting fossil fuels. Various technologies have been introduced to form bioethanol from lignocellulosic biomass. Seed pods of Bombax ceiba, which are produced and wasted in large amount annually, were used as a source of cellulose. In this study, response surface methodology was used to explore the effects of KOH concentrations, substrate loading, and residence time on cellulose exposure and liberation of reducing sugars (RS), total sugars (TS), and total phenolic compounds from seed pods of B. ceiba. Box-Behnken design with three variables and three levels showed maximum release of total phenolic compounds (394.04 mg/ml) and RS (50.06 mg/ml) corresponding to 3% KOH concentration, 15% substrate level with residence time of 8 h at 121 degrees C, and maximum cellulose exposure (64%), and TS (206.65 mg/ml) liberation was observed at 5% KOH concentration and 10% substrate level at same temperature for same soaking time. While at room temperature maximum cellulose exposed (46%), TS (146.1480 mg/ml), total phenol (300.3901 mg/ml), and RS (9.0075 mg/ml) were observed at 3% KOH, 15% substrate concentration, and 8-h residence time. These results suggested that thermochemical pretreatment is more effective than chemical pretreatment alone. The second-order polynomial equation using analysis of variance was employed for analyzing the results.