Abstract: Phototherapy has emerged as a research hotspot in cancer treatment owing to its advantages of high selectivity and low invasiveness; however, the wavelength range and targeting precision of dyes remain key bottlenecks limiting their clinical application. Taking advantage of the heavy-atom effect, this study used flavonoid dyes as the parent structure and developed a novel long-wavelength dye M-Se-F-N via structural modification by substituting oxygen atoms with selenium atoms, thereby providing a new solution for the upgrading of photothermal therapy technology. The dye adopts a D-π-A conjugated structure, and its maximum absorption wavelength exceeds 800 nm after specific binding to RNA, which effectively covers the near-infrared theranostic window. By leveraging the physiological characteristic of high RNA expression in cancer cells, M-Se-F-N can achieve precise enrichment at tumor sites, and under excitation with an 808 nm laser, it rapidly elevates the local temperature to approximately 53 ℃, which falls within the effective therapeutic range, enabling highly selective photothermal ablation of HeLa cells with minimal off-target toxicity. Furthermore, this dye exhibits excellent photothermal stability and good biocompatibility, and through structural innovation, this work breaks through the performance limitations of traditional flavonoid dyes, provides new insights into the development of photothermal agents with both targeting capability and high safety, and holds promising potential for promoting the clinical translation of phototherapy in the precise treatment of hypoxic tumors.