Photocatalytic therapy for hypoxic tumors often suffers from inefficiencies due to its dependence on oxygen and the risk of uncontrolled activation. Inspired by the oxygen-independent and precisely regulated photocatalytic functions of natural light-harvesting chlorosomes, chlorosome-mimetic nanoreactors, termed Ru-Chlos, are engineered by confining the aggregation of photosensitive ruthenium-polypyridyl-silane monomers. These Ru-Chlos exhibit markedly enhanced photocatalytic performance compared to their monomeric counterparts under acidic conditions, while notably bypassing the consumption of oxygen or hydrogen peroxide. The photocatalytic activity of Ru-Chlos is finely tunable through light-responsive disassembly of the Ru-bridged matrix, with tunability governed by pre-irradiation duration. Utilization of Ru-Chlos loading prodrug [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS) for phototherapy facilitates the generation of toxic radicals (oxABTS) and the photocatalytic conversion of endogenous NADH to NAD⁺, inducing oxidative stress in hypoxic cancer cells. Simultaneously, the light-responsive degradation of Ru-Chlos produces Ru-based toxins that further contribute to the therapeutic effect. This dual-action mechanism elicits potent immunogenic cell death effects and significantly enhances antitumor efficacy with the aid of a PD-l blockade. These biomimetic chlorosomes highlight their potential to advance oxygen-independent photocatalytic nanoreactors with controlled activity for novel cancer photoimmunotherapy strategies.