Plasmonic nanomaterials, especially a wide variety of gold nanoparticles, demonstrate great potential for theranostics of cancer. Herein, a gold nanotriangle with CD133 and hyaluronic acid on its surface loaded with a near-infrared photosensitizer was prepared for enhanced photodynamic/ photothermal combined anti-tumor therapy. CD133 and hyaluronic acid provide the nanoprobe with dual tumor targeting, while the hyaluronic acid also protects photosensitive drugs from photodegradation. Thus, the nanoprobe has enhanced photothermal/photodynamic effects. This integrated treatment strategy significantly enhanced photodynamic/photothermal destruction of osteosarcoma cells. In addition, this treatment, induced by mild irradiation with a single wavelength laser, inhibited tumor growth in an osteosarcoma mouse model. These results indicate that this systemic treatment strategy can achieve enhanced anti-tumor therapeutic effects through active tumor targeting and protection of the loaded drugs. © 2020 IOP Publishing Ltd.