Abstract: This study aimed to explore the process of ultrasound-assisted extraction of mangiferin from mango kernels. Through single factor experiments and Box-Behnken response surface design, investigated the effects of five factors: Material liquid ratio, ethanol concentration, ultrasound temperature, ultrasound time, and ultrasound power on the extraction rate of mangiferin. The results showed that the optimal extraction parameters were as follows: Ethanol concentration of 75%, liquid-to-solid ratio of 1:50 g/mL, ultrasonic temperature of 45 ℃, ultrasonic time of 40 min, and ultrasonic power of 288 W. Under this optimal process condition, the yield of mangiferin was 4.78%, with a predicted value of 4.75%. This study can provide a theoretical reference for the extraction of mangiferin from mango kernels.