A multifunctional drug delivery system (GNRs@mSiO2-HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO2) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO2-HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8％. It also has pH-enzyme sensitive and NIR-triggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO2-HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@mSiO2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO2-HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO2-HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.