Ground cotton stalks were pretreated with sodium hydroxide (NaOH) at concentrations of 1-4% (w/v), pressures of 30-130 kPa, durations of 15-75 min, and liquid/solid ratios of 10:1-30:1. Modeling of the high pressure assist-alkali pretreatment (HPAP) of cotton stalk was attempted. The levels of NaOH concentration, pressure, and duration were optimized using a Box-Behnken design to enhance the cellulose content of treated solid residue. The optimum pretreatment conditions were as follows: liquid/solid ratio, 20:1; pressure, 130 kPa; NaOH concentration, 3.0%; duration, 40 min. During the conditions, cellulose content of pretreated cotton stalk residue was 64.07%. The maximum cellulose conversion of 45.82% and reducing sugar yield of 0.293 g/g upon hydrolysis were obtained. Significant differences were observed in biomass composition and physiochemical characteristics between native and alkali-treated biomass. High NaOH concentration and pressure were conducive to lignin dissolution and resulted in increased cellulose content and conversion. (C) 2013 Elsevier Ltd. All rights reserved.