Novel supramolecular system of amphiphilic hyperbranched polymer with hyperbranched poly(beta-cyclodextrin) core was designed and synthesized to accomplish a so-called selective encapsulation, where two types of guest molecules can be encapsulated into two types of molecular cavities from beta-cyclodextrin (beta-CD) and topography structure of hyperbranched polymer, respectively. The double molecular recognition behaviors from beta-CD and hyperbranched cavities drive one guest to go into the former, the other guest to the latter. This selective encapsulation was further confirmed via the release profiles and sequences of Levofloxacin lactate (LL) and Phenolphthalein (PP). LL presents a sustained release period followed by an almost non-release stage, while PP releases on a quite slow rate at first, subsequently on the linearly increasing rate. At the early stage, the release of LL dominates in comparison with PP, and then the release rate of PP increases to play a determinate role in the release system. It can be attributed to the existence of two guests in the different molecular cavities with the different microenvironments. The observed selective encapsulation of supramolecular system is a new phenomenon, which is helpful to extend the application of CD-based hyperbranched polymers in supramolecular science and complex drug delivery system. (C) 2010 Elsevier Ltd. All rights reserved.