In the treatment of cancers, molybdenum disulfide (MoS2) has shown great potential as a photoabsorbing agent in photothermal therapy and also as an antitumor drug delivery system in chemotherapy. However, the poor dispersibility and stability of MoS2 in aqueous solutions limit its applications in cancer therapy. To overcome the shortcomings, MoS2 was modified mainly by surface adsorption of linear polymers, such as chitosan and poly(ethylene glycol). As reported, the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts. Herein, we developed hyperbranched polyglycidyl (HPG)-modified MoS2 (MoS2-HPG) by absorbing HPG on the MoS2 surface. The MoS2-HPG as a novel photoabsorbing agent was also used as a nanoscaled carrier to load antitumor drug doxorubicin hydrochloride (DOX) (MoS2-HPG-DOX) for combined chemo-photothermal therapy. The physicochemical and photothermal properties of MoS2-HPG were measured, and the results indicate that MoS2-HPG had good dispersion and stability in aqueous solutions and also high photothermal conversion efficiency. MoS2-HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro. Furthermore, the combined chemo-photothermal therapy using MoS2-HPG-DOX demonstrated better anticancer effect than the individual chemotherapy or photothermal therapy alone. From the results, MoS2-HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment.