Graphene quantum dots (GQDs)-decorated hollow copper sulfide nanoparticles (CuS NPs) were developed as a multifunctional platform for controlled intracellular drug release and enhanced photothermal-chemotherapy. The CuS NPs were firstly synthesized to encapsulate anticancer drug doxorubicin (DOX) followed by the GQDs decoration on the surface of CuS NPs. The prepared NPs exhibited good crystal structure, uniform nanosize, excellent colloidal stability, high drug encapsulation and enhanced optical absorbance. Moreover, the drug release was successfully triggered from the DOX-CuS@GQDs NPs under high temperature and (near-infrared) NIR laser irradiation. Encouraged by this result, we moved to investigate the intracellular drug release behavior under NIR laser irradiation on MDA-MB-231 cells. The confocal images and flow cytometry analysis indicated a significant NIR-triggered DOX release within MDA-MB-231 cells after cellular uptake. Furthermore, the CuS NPs could readily convert light energy to heat to photothermally ablate the cancer cells under NIR laser irradiation, and the photothermal ablation effect was further enhanced by the capping of GQDs on CuS NPs. The combined photothermal therapy and chemotherapy of the prepared DOX-CuS@GQDs NPs also enabled a synergistic therapeutic effect on cancer cells. Therefore, the prepared DOX-CuS@GQDs NPs provided a novel promising platform for cancer therapy with controlled intracellular drug release and combined photothermal-chemotherapy.