OBJECTIVE: To optimize the ethanol precipitation technology of Crataegus pinnatifida and provide reference for the production process control of C. pinnatifida preparation. METHODS: Plackett-Burman design was used to investigate the effects of technology parameters on retention rate of total flavonoids of C. pinnatifida, such as stirring speed, flow speed of ethanol, ethanol precipitation time, ethanol volume fraction, ethanol-solid ratio, density of concentration liquid before ethanol precipitation and static temperature. Box-Behnken response surface methodology was used to optimize critical technology parameters, and validation test was also conducted. RESULTS: The optimal key parameters for ethanol precipitation technology of C. pinnatifida included density of concentration liquid before ethanol precipitation 1.04 g/mL, ethanol-solid ratio 2.86 ∶ 1(mL/g), stirring speed 185 r/min. After validation, under the optimal technology parameters, average retention rate of total flavonoids of C. pinnatifida was 89.74%(n=3), relative error of which to predicted value 91.40% was 1.85%. CONCLUSIONS: Box-Behnken response surface methodology optimize ethanol precipitation technology of C. pinnatifida. It is simple and feasible.