In this study, the extrusion detoxification technique on flaxseed was investigated by uniform design optimization. The effect of the temperature (◦C), the feeding rate (kg h−1), the screw speed (rpm) and the moisture content (%) on the response value (the removal rate, %) of hydrocyanic acid (HCN) in flaxseed has been investigated. U12 (123×4) mixed-level uniform design was selected and the equation of extrusion detoxification model was obtained after 12 experimentations. The content of cyanide in flaxseed was determined by Association of Official Analytical Chemists (AOAC) method. The extrusion detoxification technique was optimized with stepwise non-linear regression analysis and response surface method (RSM). DPS Professional V.3.01 and MATLAB (Version 6.5.1) were used for data analysis. The optimized results, including the temperature, the feeding rate, the screw speed, the moisture content of flaxseed, the optimized value and the relative error of the model, were 146.0℃, 32.7 kg h−1, 152.5 rpm, 12.5, 93.23 and 1.76%, respectively. In order to improve the productivity, the feeding rate can be increased to 60 kg h−1on condition that it can reach the demanding value of detoxification. At this feeding rate, the model value of the removal rate of HCN in flaxseed is 84.38%; the experimental value is 83.32%; the relative error of the model is 1.27%.