As a prominent class of 2D transition metal dichalcogenides (TMDCs), niobium diselenide nanosheets (NbSe NSs) have garnered tremendous interest on account of promising applications pertaining to optoelectronics and energy storage. Although NbSe NSs have many unique advantages such as inherent biocompatibility and broad absorption in the NIR region, their biomedical applications have rarely been reported, especially as therapeutic agents for the second near-infrared (NIR-II) range. Herein, a biodegradable nanotherapeutic platform consisting of NbSe NSs is designed and demonstrated for NIR-II light-triggered photothermal therapy. NbSe NSs synthesized by grinding and liquid exfoliation exhibit superior photothermal conversion efficiency (48.3%) and remarkable photothermal stability in the NIR-II region. In vitro assessment demonstrates that NbSe NSs have favorable photothermal cell ablation efficiency and biocompatibility. After intravenous injection in vivo, the NbSe NSs accumulate passively in tumor sites to facilitate fluorescence imaging and tumor ablation by NIR-II illumination. Furthermore, as a result of gradual degradation in the physiological environment, NbSe NSs can be excreted from the body to avoid potential toxicity caused by long-term retention in vivo. The results reveal a promising NIR-II light-triggered PTT strategy with the aid of NbSe NSs and the platform is expected to have large potential in cancer theranostics.