Inducing oxidative stress through metal ions activated biocatalysis is a fundamental mechanism of metal ion-interference therapy (MIIT). However, the actual catalytic efficiency of MIIT is often limited by the random valence states of metal ions and scattered space. Herein, copper-iron bimetallic sulfide nanoparticles coated with bovine serum albumin (CFS NPs) are synthesized through metal ion valence modulation strategy. Significant amounts of Cu⁺ and Fe²⁺ were released by CFS NPs, which is crucial for catalyzing Fenton-like reaction. The presence of Fe³⁺ further boosts Fe²⁺ availability and protects against hydroxyl radical (•OH) elimination via glutathione (GSH) consumption, amplifying the mitochondrial oxidative stress to induce apoptotic cell death. This oxidative stress damage is manifested in Cu