Abstract: OBJECTIVE To optimize the process of extracting flavonoids from Euphorbia lunulata Bge by ionic liquid assisted ultrasonic method, and provide a basis for further extraction of flavonoids in Euphorbia lunulata Bge. METHODS Using ionic liquid as extraction solvent, extract flavonoids from Euphorbia lunulata Bge assisted with ultrasound method. The species and concentration of ionic liquids, the ratio of total volume of extracted solvent and the mass of medicinal materials, ultrasonic time, ultrasonic temperature were changed in turn. Taking the flavonoid extraction rate as the index, the optimal conditions of the single factor were determined, optimize the optimal extraction conditions based on the single factor experimental results combined with the responsive surface design. The contents of kaempferol and hypericin were then determined by HPLC to investigate the changes of different ionic liquids on flavonoid extraction in Euphorbia lunulata Bge. RESULTS The optimum extraction conditions: the type of ionic liquid was 1-butyl-3-methylimidazole bromide, the volume ratio of ionic liquid to alcohol was 1∶6, the ratio of the total volume of the extracted solvent to the mass of the medicinal material was 50∶1, the temperature was 40 ℃, and the ultrasonic time was 1 h. The extraction rate was (15.8±0.9)% under the optimal conditions, which was significantly increased compared to the conventional extraction rate of 5.14%. CONCLUSION It is feasible to extract flavonoids from Euphorbia lunulata Bge by using ionic liquid as solvent. Flavonoid extraction rate is not positively correlated with the carbon chain length of the ionic liquid parent nucleus.