Nanodelivery of antitumor drugs is a new treatment mode for cancer. The aim of this investigation was to construct and evaluate a facile nanodelivery platform for individualized antitumor drugs based on functionalized hyperbranched poly(ether-ester)s. Poly(ether-ester)s, as a kind of hyperbranched polymers, have received extensive attention. Three terminal-functionalized (OH–, NH2– and COOH–) hyperbranched poly(ether-ester)s were prepared and characterized by dynamic light scattering and attenuated total reflectance Fourier transform infrared spectroscopy. The relationship between chemical terminal variation and physical surface charges was investigated. Biocompatibility of these polymers was confirmed by methyl tetrazolium assays and scanning electron microscopy. As a model drug, pingyangmycin has antitumor and antiangiogenic effects. In the paper, pingyangmycin was mixed with carboxyl-modified hyperbranched poly(ether-ester) through ionic binding. Polymer-mixed pingyangmycin exhibited significant inhibition of HN-6 head and neck cancer human cellsin vitro. These studies demonstrate that functionalized hyperbranched (ether-ester)s can be exploited as a facile nanodelivery platform for antitumor therapy.