In recent years, the coupling of structurally and functionally controllable polymers with biologically active peptide materials to obtain polymer-peptide hybrids with excellent properties and biocompatibility has led to important research progress in the field of polymers. In this study, a pH-responsive hyperbranched polymer hPDPA was prepared by combining atom transfer radical polymerization (ATRP) with self-condensation vinyl polymerization (SCVP) using a three-component reaction of Passerini to obtain a monomeric initiator ABMA containing functional groups. The pH-responsive polymer peptide hybrids hPDPA/PArg/HA were obtained by using the molecular recognition of polyarginine (β-CD-PArg) peptide modified with β-cyclodextrin (β-CD) on the hyperbranched polymer, followed by the electrostatic adsorption of hyaluronic acid (HA). The two hybrid materials, h1PDPA/PArg12/HA and h2PDPA/PArg8/HA could self-assemble to form vesicles with narrow dispersion and nanoscale dimensions in phosphate-buffered (PB) at pH = 7.4. The assemblies exhibited low toxicity as drug carriers of β-lapachone (β-lapa), and the synergistic therapy based on ROS and NO generated by β-lapa had significant inhibitory effects on cancer cells.