Abstract: In order to study the optimal extraction process of antioxidants from Malus hupehensis leaves, hydroxyl radical scavenging rate was taken as a reference index, and the extraction conditions of antioxidants from Malus hupehensis leaves was studied by response surface optimization ultrasonic-assisted enzymatic method. The results showed that the best process of ultrasonic-assisted enzyme method was 100 W ultrasonic power, liquid to material ratio 17:1 mL∙g⁻¹, ultrasonic time 32 min, cellulase addition 2.6%, enzymatic digestion time 49 min. The hydroxyl radical scavenging rate was 89.9%±0.06% under this condition, the flavonoid content in the extract was 14.01%, the polyphenol content was 8.93%, and the polysaccharide content was 7.65%, compared with the decoction method, reflux method, enzymatic method and ultrasonic method, the active substance content was increased by more than 10%, the DPPH scavenging rate and hydroxyl radical scavenging rate were increased by more than 20%. It's better to extraction of antioxidants from Malus hupehensis leaves by ultrasonic aided enzymatic method.