As a novel type of two-dimensional materials, MXenes demonstrated great potential for biomedical applications due to their excellent photothermal and photodynamic properties. However, their exposed unmodified surface cannot ensure sufficient stability for MXene in a biological environment. Here, we developed an efficient method to modify the surface of MXenes in aqueous medium. A water-soluble initiator was designed and covalently anchored onto MXene surfaces, which was used to initiate copper(I)-catalyzed atom transfer radical polymerization to introduce a layer of water-soluble polyacrylamide on MXene surfaces (PAM-MXenes). Impressively, it was found that the grafting of the polymer layer on MXene surfaces greatly enhanced the colloidal stability of modified MXenes which remained well dispersed in cell culture medium for over 7 days and for over one month in water without aggregation or sedimentation. Furthermore, their photothermal properties were not influenced as the PAM-MXenes demonstrated uncompromised heat-generating capacities upon irradiation at 808 nm nor did they cause marked toxicity to cells. Thus, our work provided an effective approach to ameliorate the surface properties of MXene materials.