Abstract: In this study,Majiayou grapefruit peel was used as the research object,and the extraction process of total flavonoids in grapefruit peel was optimized by enzyme-assisted ultrasonic method. Firstly,the effects of complex enzyme ratio,enzyme dosage,pH,solid-liquid ratio,enzymatic hydrolysis temperature,enzymatic hydrolysis time,ultrasonic power and ultrasonic time on the yield of total flavonoids in grapefruit peel were studied. On this basis,the factors of significant effects were determined by the Plackett-Burnman experiment:Enzyme dosage,enzymatic hydrolysis temperature,ultrasonic power and ultrasonic time. Then Box-Behnken experimental design was used to optimize the total flavonoids in grapefruit peel. The results showed that the extraction conditions of total flavonoids in grapefruit peel by enzyme-assisted ultrasonic method were as follows:Enzyme ratio 3:2,enzyme dosage 1.70%,pH4.5,ratio of material to liquid 1:20 g/mL,enzymatic hydrolysis temperature 55.0 ℃,the enzymatic hydrolysis time was 60 min,the ultrasonic power was 183.00 W,and the ultrasonic time was 41.00 min. Under these conditions,the total flavonoid yield in grapefruit peel was 2.19%.