Hydrogen sulfide (H 2S) has been considered as the third biologically gaseous messenger (gasotransmitter) after nitric oxide (NO) and carbon monoxide (CO). Fluorescent detection of H 2S in living cells is very important to human health because it has been found that the abnormal levels of H 2S in human body can cause Alzheimer’s disease, cancers and diabetes. Herein, we develop a cyclodextrin-based metal-organic nanotube, CD-MONT-2, possessing a {Pb 14} metallamacrocycle for efficient detection of H 2S. CD-MONT-2′ (the guest-free form of CD-MONT-2) exhibits turn-on detection of H 2S with high selectivity and moderate sensitivity when the material was dissolved in DMSO solution. Significantly, CD-MONT-2′ can act as a fluorescent turn-on probe for highly selective detection of H 2S in living cells. The sensing mechanism in the present work is based on the coordination of H 2S as the auxochromic group to the central Pb(II) ion to enhance the fluorescence intensity, which is studied for the first time.