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Manipulating Fenton chemistry in tumor microenvironment (TME) for the generation of reactive oxygen species is an effective strategy for chemodynamic therapy. However, this is usually restricted by limited intracellular content of H 2 O 2 and insufficient acidic environment at the tumor site. Herein, a ferric metal-organic framework (MOF) is covalently grafted with a prodrug of cisplatin (Pt(IV) prodrug) and loaded with a biocatalyst glucose oxidase (GOx) to afford a nanozyme MOF-Pt(IV)@GOx for cascade reactions. In this system, the attached Pt(IV) prodrug on MOF plays a significant role in the cooperative enhancement of GOx loading and chemotherapy. The high concentration of glutathione in TME reduces Fe(III) to Fe(II) for Fenton reaction, and converts Pt(IV) prodrug to cisplatin for DNA targeting and H 2 O 2 production. Meanwhile, glucose oxidation catalyzed by GOx not only consumes glucose for starvation therapy, but also promotes the intracellular acidity and H 2 O 2 supply in TME, which are in favor of Fenton reaction. Both in vitro and in vivo studies demonstrate that MOF-Pt(IV)@GOx enables remarkable anticancer efficacy due to the synergistic trimodal therapy consisting of ferroptosis, starvation therapy, and chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)