Hawthorn seed (HS), an important by-product of the Hawthorn industry, is rich in potentially health-promoting flavonoids compounds. In this paper, the ultrasound-assisted extraction (UAE) of FC from HS was investigated. Important variables and their levels were obtained using Plackett-Burman (PB) design and Box-Behnken (BB) design. A mathematical model was developed to show the effects of each variable and their combinatorial interactions on extraction yield of FC. A high coefficient of determination (R(2) = 91.26%) indicated good agreement between the experimental and predicted values of FC yield. The optimum levels of these significant parameters were determined using response surface methodology (RSM), which revealed these as follows: ultrasound temperature 65 °C, ultrasonic time 37 min, extraction temperature 91 °C, extraction time 1.5h, solid-liquid ratio of 1:18, and 72% ethanol. Under the optimum condition, the UAE rate of FC was up to 91.7%, and the yield of FC was 16.45 ± 0.02 mg/g (P