In this paper, a redox-triggered drug delivery system of DOX/MSN-Au was prepared for chemo-photothermal synergistic therapy. The ultra-small gold nanoparticles (NPs) were appended to the openings of mesoporous silica nanoparticles (MSN) by Au-S bonds as the gatekeepers. Meanwhile, the gold NPs could be heated to high temperature by the near infrared (NIR) light irradiation, which is conducive to photothermal therapy. X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectrometer (FT-IR) spectra confirmed the formation of MSN-SH and MSN-Au. An in vitro NIR-induced photothermal study indicated that MSN-Au possessed concentration-dependent and power-dependent photothermal conversion capacity. Doxorubicin (DOX) was selected as the model drug loaded in the MSN. In vitro drug release showed that DOX released faster in the presence of glutathione (GSH) or NIR laser irradiation than without GSH or NIR irradiation, which suggested that the system had potentials for redox-responsive and NIR-triggered drug release. Confocal Laser Scanning Microscope (CLSM) was performed to evaluate the cellular uptake performance of DOX/MSN-Au. The cytotoxicity assay indicated that DOX/MSN-Au had a synergistic therapeutic effect by the combination of chemotherapy and photothermal therapy. This work suggested that MSN-Au could be explored as a redox-triggered drug delivery system for the chemo-photothermal synergistic therapy.