Photothermal ablation (PTA) therapy has a great potential to revolutionize conventional therapeutic approaches for cancers, but it has been limited by difficulties in obtaining biocompatible photothermal agents that have low cost, small size (<100 nm), and high photothermal conversion efficiency. Herein, we have developed hydrophilic plate-like Cu₉S₅ nanocrystals (NCs, a mean size of ∼70 nm × 13 nm) as a new photothermal agent, which are synthesized by combining a thermal decomposition and ligand exchange route. The aqueous dispersion of as-synthesized Cu₉S₅ NCs exhibits an enhanced absorption (e.g., ∼1.2 × 10⁹ M^–1 cm^–1 at 980 nm) with the increase of wavelength in near-infrared (NIR) region, which should be attributed to localized surface plasmon resonances (SPR) arising from p-type carriers. The exposure of the aqueous dispersion of Cu₉S₅ NCs (40 ppm) to 980 nm laser with a power density of 0.51 W/cm² can elevate its temperature by 15.1 °C in 7 min; a 980 nm laser heat conversion efficiency reaches as high as 25.7%, which is higher than that of the as-synthesized Au nanorods (23.7% from 980 nm laser) and the recently reported Cu_2–xSe NCs (22% from 808 nm laser). Importantly, under the irradiation of 980 nm laser with the conservative and safe power density over a short period (∼10 min), cancer cells in vivo can be efficiently killed by the photothermal effects of the Cu₉S₅ NCs. The present finding demonstrates the promising application of the Cu₉S₅ NCs as an ideal photothermal agent in the PTA of in vivo tumor tissues.