The semiconductor compounds have been proven to be promising candidates as a new type of photothermal therapy agent, but unsatisfactory photothermal conversion efficiencies limit their widespread application in photothermal therapy (PTT). Herein, we synthesized cysteine-coated CuS nanoparticles (Cys-CuS NPs) as highly efficient PTT agents by a simple aqueous solution method. The Cys-CuS NPs have a good biocompatibility owing to their biocompatible cysteine coating and exhibit a strong absorption in the near-infrared region due to the localized surface plasma resonances of valence-band free carriers. The photothermal conversion efficiency of Cys-CuS NPs reaches 38.0%, which is much higher than that of the recently reported Cu9S5 and Cu(2-x)Se nanocrystals. More importantly, tumor growth can be efficiently inhibited in vivo by the fatal heat arising from the excellent photothermal effect of Cys-CuS NPs at a low concentration under the irradiation of a 980 nm laser with a safe power density of 0.72 W cm(-2). Therefore, the Cys-CuS NPs have great potential as ideal photothermal agents for cancer therapy.