Abstract: In this paper, the optimum conditions for the extraction of total flavonoids from Walnut shell were determined using response surface methodology. On the basis of single-factor experiments, selecting extraction temperature, ethanol concentration and liquid-to-solid ratio as independent variables, response surface methodology was applied to investigate the effect of three variables on extraction yield of total flavonoids. A regression model describing extraction content of total flavonoids as a function of these three variables was established. The optimal conditions for achieving the high extraction rate of total flavonoids from Walnut shell were ethanol concentration of 59%, extraction temperature of 78℃ and liquid-to-solid ratio of 33:1. The result of verification experiment was coincided with predictive value, the content of total flavonoids from Walnut shell was 3. 61mg·g-1.