Ionic liquids (ILs) solutions as green solvents were successfully applied in the ultrasonic-assisted extraction (UAE) ofBerberine fromCoptis chinensis. Aseries of 1-alkyl-3-methylimidazoliumionic liquidswith different cations and anions were evaluated and compared for their extraction efficiency; the results indicated that the structure of ILs has significant influence on the extraction efficiency for target analytes. [PSMIM][H2PO4] was finally selected as the optimal IL. In addition, the concentration of the [PSMIM][H2PO4]-water solutionwas optimized.And the extraction parameters including ultrasonic power, extraction time and solidÂliquid ratio were all optimized by response surface method also. Moreover, the extraction mechanism was discussed. Compared with the lixiviating method with dilute H2SO4 and regular UAE with MeOH, the approach gained higher extraction efficiency, reduced the extraction time and pollution.