Background: Carbon-based drug delivery systems have attracted great interest because of their excellent photothermal conversion capability and high specific surface area for drug loading. Herein, we report a multifunctional nanoplatform based on hyaluronic acid (HA)-modified and graphene quantum dot (GQD)-gated hollow mesoporous carbon nanoparticle (HMCN) for anticancer drug encapsulation and targeted chemo-photothermal therapy of CD44 receptor-overexpressed cancer cells. Methods: In this design, HMCN was not only used as a nanocarrier with high drug loading content to achieve chemotherapy, but also as a near-infrared absorbing agent to realize photothermal therapy. GQDs could not only prevent premature drug release during blood circulation, but also enhance the chemo-photothermal therapeutic efficacy for complete tumor growth suppression. After being modified with HA, the HA-HMCN(DOX)@GQDs could specifically target cancer cells. Results: As expected, the as-prepared HMCN exhibited high doxorubicin (DOX)-loading capacity of 410 mg/g and excellent light-to-heat conversion property. The DOX was released from HA-HMCN(DOX)@GQDs in a near-infrared laser and pH stimuli-responsive manner, which could enhance the therapeutic effect. In vitro cell biological experimental results confirmed that the nanoplatform possesses excellent biocompatibility, specifically target CD44 receptor-overexpressing human cervical carcinoma HeLa cells, and has remarkable synergistic chemo-photothermal killing capacity. The in vivo therapeutic studies in HeLa xenografts also showed negligible toxicity of [email protected] and complete inhibition of tumor growth of HA-HMCN(DOX)@GQDs with near-infrared irradiation. Conclusion: The excellent therapeutic effects demonstrated in vitro and in vivo suggested the HMCN-based nanoplatform holds potential for efficient dual-responsive targeting drug delivery and synergistic chemo-photothermal therapy. © 2018 Fang et al.