Nanographene oxide (NGO) are highly suitable to be the shells of inorganic nanomaterials to enhance their biocompatibility and hydrophilicity for biomedical applications while retaining their useful photonic, magnetic, or radiological functions. In this study, a novel nanostructure with gold nanorods (AuNRs) encapsulated in NGO shells is developed to be an ultraefficient chemophotothermal cancer therapy agent. The NGO shells decrease the toxicity of surfactant-coated AuNRs and provide anchor points for the conjugation of hyaluronic acid (HA). The HA-conjugated NGO-enwrapped AuNR nanocomposites (NGOHA-AuNRs) perform higher photothermal efficiency than AuNRs and have the capability of targeting hepatoma Huh-7 cells. NGOHA-AuNR is applied to load doxorubicin (DOX), and it exhibits pH-responsive and near-infrared light-triggered drug-release properties. Chemophotothermal combined therapy by NGOHA-AuNRs-DOX performs 1.5-fold and 4-fold higher targeting cell death rates than single chemotherapy and photothermal therapy, respectively, with biosafety to nontargeting cells simultaneously. Furthermore, our strategy could be extended to constructing other NGO-encapsulated functional nanomaterial-based carrier systems.