A hydrothermal process using subcritical water and ethanol as an extraction solvent has been studied to extract high-value flavonoid compounds from Quercus leaves. The univariate analysis showed that the maximum quercetin yield was 34.6 mg/g obtained at the liquid-solid ratio of 30:1 ml/g, concentration of ethanol 60% (V/V), extraction temperature of 180 C, and extraction duration of 5 h. Based on the Box-Behnken experiment design, the response surface methodology (RSM) was used to optimize the liquid-to-solid ratio, extraction time, extraction temperature, ethanol concentration, and other operating conditions of hydrothermal extraction of quercetin. The regression equation showed that the maximum yield of quercetin was 36.1 mg/g under the conditions of solvent ethanol concentration of 65% (V/V), liquid-solid ratio of 40:1 ml/g, extraction temperature of 189 C, and extraction duration of 5.5 h. The quercetin yield of 36.1 mg/g obtained by the hydrothermal method was 5.6 times the 6.4 mg/g obtained by the traditional ethanol reflux extraction at the same concentration of ethanol 65% (V/V), liquid-solid ratio of 40:1 ml/g, and extraction duration of 5.5 h, but at the boiling point of the solvent.