Intracellular redox dyshomeostasis promoted by tumor microenvironment (TME) modulation has become an appealing therapeutic target for cancer management. Herein, a dual plasmonic Au/SF@CuS nanoreactor (abbreviation as ASC) is elaborately developed by covalent immobilization of sulfur defective CuS nanodots onto the surface of silk fibroin (SF)-capped Au nanoparticles. Tumor hypoxia can be effectively alleviated by ASC-mediated local oxygenation, owing to the newfound catalase-mimic activity of CuS. The semiconductor of CuS with narrow bandgap energy of 2.54 eV enables a more rapid dissociation of electron-hole (e/h) pair for a promoted US-triggered singlet oxygen (O) generation, in the presence of Au as electron scavenger. Moreover, CuS is devote to Fenton-like reaction to catalyze HO into ·OH under mild acidity and simultaneously deplete glutathione to aggravate intracellular oxidative stress. In another aspect, Au nanoparticles with glucose oxidase-mimic activity consumes intrinsic glucose, which contributes to a higher degree of oxidative damage and energy exhaustion of cancer cells. Importantly, such tumor starvation and O yield can be enhanced by CuS-catalyzed O self-replenishment in HO-rich TME. ASC-initiated M1 macrophage activation and therapy-triggered immunogenetic cell death (ICD) favors the systematic tumor elimination by eliciting antitumor immunity. This study undoubtedly enriches the rational design of SF-based nanocatalysts for medical utilizations.