We report photoswitchable fluorescent hemithioindigos (HTIs) where the metastable E isomers were stabilized by the proton-bridged intramolecular hydrogen bond. Titration experiments and computational analysis indicated that the E isomers were much more basic than the Z isomers, which enabled photoactivated colorimetric and fluorescent pH response in solvents and polypropylene films. The HTIs exhibited reversibly switchable fluorescence with the Z isomers being the most fluorescent. Moreover, the HTIs were lysosomotropic and the kinetic fluorescence evolution during photoswitching was able to differentiate subcellular compartments with different pH. The combination of photoenhanced basicity, switchable fluorescence, and proton-coupled photochromism lay the groundwork for a broad range of chemical and biological applications.