Bioactive cellulose-based hydrogels (CBHs) have shown significant potential in cancer treatment through various therapeutic strategies. This chapter highlights recent advances in the functionalization of CBHs to impart key physical, chemical, and biological properties, such as injectability, biocompatibility, biocatalytic activity, and targeted recognition, which facilitate their application in tumor chemotherapy, chemodynamic therapy, photothermal therapy, photodynamic therapy, and immunotherapy. Additionally, the underlying mechanisms by which CBHs exert therapeutic effects are discussed to emphasize their advantages in achieving high-performance cancer treatment. This chapter aims to provide readers with a comprehensive understanding of the design and modification strategies used to enhance CBH functionality, thereby broadening their biomedical applications in areas such as tissue engineering, antibacterial coatings, and biosensing.