Ionic liquid-based ultrasonic-assisted extraction (IL-UAE) was developed to extract and separate the isochlorogenic acid C (ICGA) from a cultivar of Chrysanthemum morifolium (Chrysanthemummorifolium Ra Tnat.). The influencing parameters, including IL concentration, liquid-to-solid ratio, and ultrasonic time, were optimized using response surface methodology. Of the ILs studied, 1-butyl-3-methylimidazolium bromide [(Bmim)Br] exhibited the best extraction ability. The optimized conditions included liquid-to-solid ratio of 23.44:1, ultrasonic time of 48.99 min, and IL concentration of 0.65 mol/L. Under the optimal conditions, the extraction yield of ICGA could reach to 4.20 mg/g. An aqueous two-phase system was applied for purification and separation of ICGA. The maximum extraction efficiency of 98.18% was obtained under the conditions of (NH4)(2)SO4 of 4.5 g, pH of 3.0, and a temperature of 20 degrees C at aqueous solution. Furthermore, the thermodynamic parameters showed that the purification of ICGA from salt-rich phase to IL-rich phase was a spontaneous and exothermic process. The results indicated that the proposed system is simple, rapid, and effective to serve as a viable and sustainable platform for the extraction and purification of ICGA from Chrysanthemum morifolium flowers.