Recently, the chemo-photothermal synergistic therapy has become a potential method for cancer treatment. Herein, we developed a multifunctional nanomaterial for chemo-photothermal therapeutics based on silica and graphene core/shell structure (SiO2@GN) because of the ability of GN to convert light energy into heat. Serum protein was further modified onto the surface of GN (SiO2@GN-Serum) to improve the solubility and stability of GN-based nanoparticles in physiological conditions. The as-synthesized SiO2@GN-Serum nanoparticles (NPs) have been revealed to have high photothermal conversion efficiency and stability, as well as high storage and release capacity for anticancer drug doxorubicin (SiO2@GN-Serum-Dox). The therapeutic efficacy of SiO2@GN-Serum-Dox has been evaluated in vitro and in vivo for cervical cancer therapy. In vitro cytotoxicity tests demonstrate that SiO2@GN-Serum NPs have excellent biocompatibility. However, SiO2@GN-Serum-Dox NPs show higher cytotoxicity than SiO2@GN-Serum and free Dox under irradiation with NIR laser at 1.0 W/cm(2) for 5 min owing to both SiO2@GN-Serum-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, the tumor growth is significantly inhibited by chem-photothermal effect of SiO2@GN-Serum-Dox. Overall, compared with single chemotherapy or photothermal therapy, the combined treatment demonstrates better therapeutic efficacy. Our results suggest a promising GN-based core/shell nanostructure for biomedical applications.