Abstract: In order to optimize the ultrasonic extraction process of total flavonoids from black mulberry, the black mulberry fruits from the picking garden of Awati Township of Korla City were used as raw materials, on the basis of single-factor experiments results, four factors, including ethanol volume fraction, extraction temperature, extraction time, and material-liquid ratio were selected to carry out the Box-Behnken center combination test, and the results were analyzed and optimized using Design-Expert 8.06 software. The results showed that the optimal extraction conditions for the total flavonoids in black mulberry were: ethanol volume fraction 60%, ex traction temperature 70 ℃,extraction time 40 min, and liquid-material ratio 30 ∶1（mL/g）. Under these conditions, the extraction amount of flavonoids from black mulberry was 9.565 mg/g. Which suggested that the extraction process parameters obtained by the response surface methodology have strong feasibility and high reliability.