摘要： Tumor cells metabolism and tumor blood vessels proliferation represent in a distinctive way compared to normal cells. The resulting tumor microenvironment will presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radicals generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption endows the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both (I and II) NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose, and then to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show the enhanced therapeutic efficacy of NIR-II over NIR-I principally due to its deeper tissue penetration and higher maximum permission exposure benefited from longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in tumor hypoxia microenvironment. The high biocompatibility and excellent anti-cancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.