Abstract: Objective: The surfactant-assisted ultrasonic extraction of total flavonoids from persimmon leaves was optimized. Methods: With the extraction rate of total flavonoids and DPPH radical scavenging rate as the double-indicator response values, the effects of surfactant type and mass fraction, liquid-to-material ratio, ultrasonic time, and ultrasonic temperature were investigated, and the Box-Behnken design-double response surface methodology was used to optimize the extraction process of total flavonoids from persimmon leaves. Results: The obtained optimal extraction process was as follows: Ethanol volume fraction of 70%, the mass fraction of sodium dodecyl sulfate 0.6%, liquid-to-material ratio of 22:1 mL/g, ultrasonic temperature of 30 ℃ and time of 7.3 min. Under these conditions, the actual extraction rate of total flavonoids from persimmon leaves was (103.63±0.10) mg/g and the DPPH radical scavenging rate was (65.35%±0.12%). Conclusion: The optimized extraction process can effectively improve the yield of total flavonoids from persimmon leaves and provide a theoretical basis for the development and utilization of flavonoids resources from persimmon leaves.