摘要： Ternary transition-metal chalcogenide nanosheets have shown great potential in diverse applications owing to their intrinsically amazing properties with broad tunable window. Direct preparation of water-soluble and biocompatible ternary chalcogenide nanosheets for theranostic application remains a challenge. In this article, we prepared Cu-Fe-Se nanosheets (CFS NSs) in an aqueous solution under ambient conditions by sequential coprecipitation method. They were functionalized with anticancer drug doxorubin (CFS@DOX) through electrostatic interactions, and labeled with radioactive isotope 99mTc through surface coordination effect. The resulting nanosheets have a size of 70 nm and a thickness of 5 nm, and can be well dispersed in water, PBS, 10% FBS, and 0.9% NaCl with an excellent colloidal stability. They also exhibit a high photothermal conversion efficiency of 78.9% for in vitro and in vivo photoacoustic imaging and photothermal therapy. The isotope-labelled nanosheets (99mTc-CFS NSs) were used for single photon emission computed tomography/computed tomography (SPECT/CT) imaging, and quantification of their blood circulation time (~4.7 h) and biodistributions in major organs, which follow an order of liver > bladder > lung > spleen > heart > kidney. The DOX functionalized nanosheets (CFS@DOX) were used for chemotherapy of cancer and exhibited excellent anti-cancer efficacy. Our research shows the great promise of ternary metal chalcogenide nanosheets for combined imaging and therapy of cancer.