The synergistic combination of polymer-inorganic hybrid nanomaterials promises a new class of vehicle systems for stimuli-responsive and cell-specific drug delivery applications. Herein, we prepared a pH-responsive and charge reversal gold -poly (bis(carboxyphenoxy) phosphazene) (PCPP) nanohybrid system exhibits excellent dispersity and stability as well as the more efficient release rate at the acidic environment. As a stimuli-responsive drug delivery vehicle, PCPP-AuNPs potentially reduces the drug loss at neutral pH, whereas rapid drug release was noticed after internalization of nanoparticles by the cancer cells. Metal nanohybrid material effectively internalized into slightly acidic cell environment and even distribution of drug in the cytoplasm and intranuclear region due to charge reversal behavior. The cytotoxicity experiments corroborated that the nanohybrid system was more efficient than the free camptothecin (CPT) due to pH quenching charge reversal behavior. In addition, CPT@PCPP-AuNPs alters cell morphology, elevates the ROS levels, apoptosis protein expression and mitochondrial dysfunction. This work provides a simple method to fabricate smart pH-responsive AuNPs for anticancer drug delivery.