Copper selenide (Cu₂₋ₓSe) nanocrystals were synthesized and coated with amphiphilic polymer to enhance their biocompatibility and hydrophilicity. These nanocrystals exhibit strong near-infrared (NIR) optical absorption with a high molar extinction coefficient of 7.7 × 10⁷ cm⁻¹ M⁻¹ at 980 nm. When excited with 800 nm light, they generate significant photothermal heating with a transduction efficiency of 22%, comparable to gold nanorods and nanoshells. In vitro experiments showed that exposure to 33 W/cm² laser light for 5 minutes led to cell death in human colorectal cancer cells (HCT-116), demonstrating the potential of Cu₂₋ₓSe nanocrystals for photothermal therapy. The nanocrystals have a hydrodynamic diameter of 39 nm and zeta potential of -40 mV, making them suitable for in vivo applications. They were found to have photothermal transduction efficiency comparable to commercial gold-based nanoparticles, with 22% for Cu₂₋ₓSe, 13% for commercial gold nanoshells, and 21% for commercial gold nanorods. The efficiency is attributed to their high absorption and low scattering properties. The nanocrystals showed no cytotoxicity up to 6 hours of exposure, and photothermal cell death was observed at 30 W/cm² laser irradiation. Cu₂₋ₓSe nanocrystals offer a promising alternative to gold-based nanoparticles for photothermal therapy due to their high efficiency, biocompatibility, and potential for targeted therapy.Copper selenide (Cu₂₋ₓSe) nanocrystals were synthesized and coated with amphiphilic polymer to enhance their biocompatibility and hydrophilicity. These nanocrystals exhibit strong near-infrared (NIR) optical absorption with a high molar extinction coefficient of 7.7 × 10⁷ cm⁻¹ M⁻¹ at 980 nm. When excited with 800 nm light, they generate significant photothermal heating with a transduction efficiency of 22%, comparable to gold nanorods and nanoshells. In vitro experiments showed that exposure to 33 W/cm² laser light for 5 minutes led to cell death in human colorectal cancer cells (HCT-116), demonstrating the potential of Cu₂₋ₓSe nanocrystals for photothermal therapy. The nanocrystals have a hydrodynamic diameter of 39 nm and zeta potential of -40 mV, making them suitable for in vivo applications. They were found to have photothermal transduction efficiency comparable to commercial gold-based nanoparticles, with 22% for Cu₂₋ₓSe, 13% for commercial gold nanoshells, and 21% for commercial gold nanorods. The efficiency is attributed to their high absorption and low scattering properties. The nanocrystals showed no cytotoxicity up to 6 hours of exposure, and photothermal cell death was observed at 30 W/cm² laser irradiation. Cu₂₋ₓSe nanocrystals offer a promising alternative to gold-based nanoparticles for photothermal therapy due to their high efficiency, biocompatibility, and potential for targeted therapy.