In the present study, ethanol/NaH2PO4 aqueous two-phase system (ATPS) was employed for the extraction and purification of flavones from honeysuckle. A Box-behnken design (BBD) was used to study the effects of salt concentration, ethanol concentration and pH on flavones partition behavior. The optimal system was found at pH 5.0, containing 4.6 g NaH2PO4 and 36% ethanol (v/v) with a K-flavones of 138 and more than 98% of the flavones in the top phase. Furthermore, the purity of flavones was enhanced from 8.86% to 22.88% by a two-step extraction, and further improved using a simple ethanol treatment to 48.73%. The ATPS showed a purity that was 4 times than that obtained by the 70% ethanol (v/v) extraction. The process turned out to be also applicable to other natural products. (C) 2013 Elsevier B.V. All rights reserved.