Abstract: Traditional methods of cancer treatment include surgery, radiotherapy, and chemotherapy. The surgical treatment is highly traumatic and easy to recur, while the period of radiotherapy is too long. Although chemotherapy is considered as the first choice to destroy tumor cells, it has obvious toxic and side effects, and the long-term chemotherapy can seriously affect the quality of the patients' life. In this study, CuS was selected as a photothermal agent, and mesoporous silica (mSiO₂) was coated on the surface of CuS using the solvothermal and template removal methods. With the aid of the large specific surface area of mSiO₂, a highly doxorubicin hydrochloride (DOX) loaded nanodrug system was prepared (CuS@mSiO₂-DOX). XRD, UV-vis, SEM, TEM, and DLS results jointly confirm that the CuS@mSiO₂-DOX nanosystem with a particle size of approximately 300-400 nm is successfully synthesized, and the loading efficiency of DOX in this system can reach up to 99.76%. The 24 h-drug release rate of CuS@mSiO₂-DOX reaches 63.44% under the conditions of pH=5.5 and 45℃, which is nearly 20 times higher than that under the normal physiological environment (pH=7.4 and 35℃), indicating that the CuS@mSiO₂-DOX nanosystem possesses obvious pH and temperature responsive release characteristics. In addition, the photothermal performance and in-vitro cytotoxicity of the CuS@mSiO₂ nanodrug delivery system was tested, and the results show that CuS@mSiO₂ exhibits a good photothermal stability with a photothermal conversion efficiency of 31.67%, and which also reveals low toxicity to normal human liver cells (HL-7702). CuS@mSiO₂ nanosystem has good biocompatibility, outstanding photothermal conversion and drug loading properties, and after DOX adsorption, the system exhibits excellent pH and laser responsive drug controlled release performance, which is expected to be widely used in the field of combining the photothermal-chemotherapy to synergistically resist tumor.