Organelle-targetedtherapy guided by fluorescence imaging is promisingfor precise cancer treatment. However, most current organelle-targetedtherapeutics can only destruct single organelles, which suffer from limited therapeutic efficacy. To address this challenge, a photoactivatableprobe was developed for sequential photodynamic destruction of multiorganellesin cancer cells, including lysosomes, lipid droplets, and mitochondria.This photoactivatable probe not only exhibits efficient cancer celleradication in vitro but also can suppress tumorgrowth in vivo. Simultaneously, the photoactivatableprobe enables sequential destruction of multiple organelles in cancercells, which can be observed in situ through theconversion of green-to-red fluorescence facilitated by a photooxidativedehydrogenation reaction. We believe this photoactivatable probe forsequential destruction of multiple organelles associated with fluorescencecolor conversion provides a new strategy for cancer treatment withgreatly improved efficacy.