Thiorhodamine-based chemodosimeter A, a disulfide linked dimer, was designed for Hg2+ recognition by virtue of the strong affinity of mercury for sulfur. Spectroscopic results reveal that chemodosimeter A exhibits real-time responses, and high sensitivity and selectivity for Hg2+ in comparison to other cations. These properties are mechanistically ascribed to the transfer from rhodamine spirolactam to the thiazoline-derived open-ring rhodamine via Hg2+ induced desulfurization. The in vitro recognition of Hg2+ in living cells pretreated with A was examined, showing that the concentration of Hg2+ that could be imaged reaches the safety limit for human beings.