Abstract: Effects of varying screw speed, moisture content and feed rate on cottonseed meal de-gossypol result were studied using a twin-screw extruder and Response Surface Methodology (RSM) was utilized to carry out the experiment design and data processing. Experimental results indicated that decreases in moisture content and feed rate, and increases in screw speed improved the de-gossypol results. Feed rate exerted the main effect on the throughput. Larger feed rate would lead to larger throughput, and thus there existed a tradeoff between a good de-gossypol result and high throughput obtained. Several response models were also put forward to approximately evaluate the influence of different processing variables. In addition, a satisfying de-gossypol result was also presented by the screw configuration used in this paper.