Chemodynamic therapy (CDT) based on the Fe-mediated Fenton reaction can amplify intracellular oxidative stress by producing toxic •OH. However, the high-dose need for Fe delivery in tumors and its significant cytotoxicity to normal tissues set a challenge. Therefore, a controllable delivery to activate the Fenton reaction and enhance Fe tumor accumulation has become an approach to solve this conflict. Herein, we report a rare-earth-nanocrystal (RENC)-based Fe delivery system using light-control techniques and DNA nanotechnology to realize programmable Fe delivery. Ferrocenes, the source of Fe, are modified on the surface of RENCs through pH-responsive DNAs, which are further shielded by a PEG layer to elongate blood circulation and “turn off” the cytotoxicity of ferrocene. The up-/down-conversion dual-mode emissions of RENCs endow the delivery system with both capabilities of diagnosis and delivery control. The down-conversion NIR-II fluorescence can locate tumors. Consequently, up-conversion UV light spatiotemporally activates the catalytic activity of Fe by shedding off the protective PEG layer. The exposed ferrocene-DNAs not only can “turn on” Fenton catalytic activity but also respond to tumor acidity, driving cross-linking and enhanced Fe enrichment in tumors by 4.5-fold. Accordingly, this novel design concept will be inspiring for developing CDT nanomedicines in the future.