Colon cancer is the third most common malignancy and the fourth most prevalent cause of death worldwide. Unfortunately, current cancer treatment approaches suffer from low specificity toward colon cancers and lack of facile imaging method to monitor a real-time therapeutic process, usually resulting in severe toxicity to normal tissues. Thus, to achieve precise therapy for colon cancer, we developed a "one-key triple-lock" bis-metal ultrathin coordination network (Gd/Cu-nanosheets) as the first H 2 S-unlocked molecular dipoles with activatable fluorescence, magnetic resonance imaging (MRI), and photodynamic effect. Notably, within noncancerous tissues, Cu ions can lock up MRI signal, fluorescent emission, and 1 O 2 generation of molecular dipoles (Gd-porphyrins). Under the trigger of endogenous H 2 S overexpressed colon cancer model (HCT116), the loss photodynamic effect of the as-disassembled Gd-porphyrin was recovered for efficient and potent killing of colon cancer cells in vivo, with minimization of toxic side effect toward normal tissue. By combining the complementary advantages of bimodal MRI/ fluorescence imaging, Gd/Cu-nanosheets enabled high-specificity visualization of colon cancer in living cells and in vivo upon activation of H 2 S. Moreover, a good correlation between the fluorescence intensity of Gd/Cu-nanosheets and cancer inhibition rates afforded the ability to self-report cancer therapeutic outcomes, thereby providing a potentially powerful tool for personalized and precise treatment of colon cancer.