Abstract: A near-infrared fluorescent small-molecule probe, a synthesis method thereof, and an application thereof are provided. The near-infrared fluorescent small-molecule probe is IR-780-F derived from IR-780, in which the basic structure of IR-780 is retained, an end of an alkyl carbon chain connected with a nitrogen (N) atom is changed by adding a trifluoromethyl group (—CF3) at the end. The IR-780-F shows excellent performance in photostability, targeting cancer cells and fluorescence imaging, and has low toxicity. It can be used for targeting tumor tissues, in vivo near-infrared fluorescence imaging, and photothermal therapy, which realizes an integration of diagnosis and treatment.