Multifunctional drug delivery systems that combine photothermal therapy and chemotherapy have become a potential approach for cancer treatment. Herein, polypyrrole (PPy), a near-infrared (NIR) light-absorbing polymer, is employed to be confined in dendrimer-like silica nanoparticles (DSNs). Then the obtained PPy@DSNs–NH₂ is further modified with biocompatible polyethylene glycol (PEG) through the reaction of –COOH and –NH₂ groups to improve its biocompatibility and stability in physiologic conditions. The as-prepared PPy@DSNs–PEG nanocomposite has been demonstrated to possess high photothermal conversion efficiency and high drug loading capacity as well as low cytotoxicity. The anticancer drug doxorubicin hydrochloride (DOX) loaded PPy@DSNs–PEG (DOX/PPy@DSNs–PEG) shows pH-responsive and heat-sensitive drug release properties. Furthermore, the in vitro cytotoxicity results display that DOX/PPy@DSNs–PEG under NIR irradiation shows the highest death rate on U251 and U87 MG cells, owing to PPy@DSNs–PEG mediated photothermal ablation and DOX-triggered cytotoxicity. Thus, the combined therapy of DOX/PPy@DSNs–PEG reveals enhanced therapeutic efficacy compared with single chemotherapy or photothermal therapy. These results indicate that the prepared multifunctional drug delivery system will be a potential candidate for biomedical applications.