The aim of this work was to evaluate cotton stalk (waste plant material after harvesting the cotton) as feedstock for bioethanol production. Different pretreatment strategies were tried using sodium hydroxide in a high pressure reactor equipped with a pitch blade turbine stirrer, followed by enzymatic hydrolysis using cellulases; the process optimization was carried out using Taguchi experimental design. Best results were achieved when the pretreatment was carried out at 180°C for 45min with mixing of substrate at 100rpm. The sugar yield was evaluated based on pretreatment severity. The hydrolysis efficiency of pretreated cotton plant waste was very good (96%), showing the excellent efficiency of the method in removing the lignin. The material balance in each stage of the process was estimated and the total process efficiency was found to be 53% based on glucose conversion.