The use of visible light to produce reactive oxygen species (ROS) from renewable water splitting is a highly promising means in photodynamic therapy (PDT). Up to date, diverse inorganic–organic hybrid materials developed as photosensitizers still undergo low therapeutic efficiency and/or poor stability. Herein, a kind of carbon-nanodot-decorated TiO nanotubes (CDots/TiO NTs) composite is developed and applied for photodynamic therapy. Upon 650 nm laser light excitation, the emissions with short wavelengths (325–425 nm) from the CDots as a result of upconversion process excite TiO NTs to form electron/hole (e/h) pairs, triggering the reaction with the adsorbed oxidants to produce ROS. Moreover, the CDots deposited on the surface of TiO NTs markedly enhance the light absorption response and narrow the band gap compared with anatase TiO nanoparticles, thereby increasing the photosensitizing efficiency. Besides, the CDots show high chemical catalytic activity for HO decomposition even if no light is needed, which is essential for PDT. The excellent therapeutic performance actuated by 650 nm light is demonstrated by in vitro and in vivo assays. This photosensitizer comprises low-cost, earth-abundant, environment-friendly merits, and especially excellent stability, implying its feasible application in biomedical field.