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Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next‐generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin‐modified MgO₂ nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg²⁺. This reaction simultaneously produces abundant H₂O₂ to induce cell death and damage the structure of transferrin to release Fe³⁺, which will react with H₂O₂ to produce highly toxic ·OH to kill tumor cells.