Cisplatin (CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate. Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment effects. Herein, chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin (BSA) stabilized gallic acid-functionalized iron nanoparticles (GA-Fe NPs) to achieve chemo/chemodynamic synergistic cascade oncotherapy. The Pt-GA-Fe NPs can be utilized to generate H₂O₂ via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) in the tumor microenvironment (TME), which would then greatly boost H₂O₂-depending chemodynamic therapy (CDT). The generated cytotoxic reactive oxygen species (hydroxyl radicals, ·OH) and the depletion of glutathione (GSH) would further promote CDDP-induced DNA damage. Moreover, benefiting from the absorption in the near-infrared (NIR) region, Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency (η = 45.5%) and allow photoacoustic imaging (PAI) guided photothermal therapy (PTT). In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic toxicity. The work highlights a new type of therapeutic agent based on CDDP with the ability of H₂O₂ self-generation, thermal responsiveness, and enhanced CDT effects for applications in cancer therapy.