Hypoxia is a huge barrier for the development of photodynamic therapy (PDT). Chemodynamic therapy (CDT) could provide a possible solution to this dilemma. In this work, a controlled Schiff-base reaction was conducted between amido groups on the surface of carbon dots (CDs) and aldehyde groups on aldehyde-modified cellulose nanocrystals (mCNCs) as well as aldehyde-mCNCs decorated with Fe₃O₄ nanoparticles. In this process, the mCNCs not only prevent the agglomeration of Fe₃O₄ but also form hydrogels with CDs. The CDs act as both photothermal agent and photosensitizer. The hypoxia could be effectively relieved through the Fenton reaction due to the addition of Fe₃O₄, and the ·OH produced in the reaction further induces CDT and enhances tumor therapy efficiency. The therapy performance was further verified through in vitro cell experiments and in vivo animal experiments. This convenient method provides inspirations for the design and preparation of advanced biomaterials with multiple functions for cancer therapy.