Biocatalysis has become a powerful tool in synthetic chemistry, where enzymes are used to produce highly selective products under mild conditions. Using photocatalytically regenerated cofactors in synergistic combination with enzymes in a cascade fashion offers an efficient synthetic route to produce specific compounds. However, the combination of enzymes and photocatalysts has been limited due to the rapid degradation of the biomaterials by photogenerated reactive oxygen species, which denature and deactivate the enzymatic material. Here, we design core-shell structured porous nano-photoreactors for highly stable and recyclable photobiocatalysis under aerobic conditions. The enzymatic cofactor NAD+ from NADH can be efficiently regenerated by the photoactive organosilica core, while photogenerated active oxygen species are trapped and deactivated through the non-photoactive shell, protecting the enzymatic material. The versatility of these photocatalytic core-shell nanoreactors was demonstrated in tandem with two different enzymatic systems, glycerol dehydrogenase and glucose 1-dehydrogenase, where long-term enzyme stability was observed for the core-shell photocatalytic system.