The S-H···S non-covalent interaction is generally known as an extremely unconventional weak hydrogen-bond in the literature. The present gas-phase spectroscopic investigation shows that the S-H···S hydrogen-bond can be as strong as any conventional hydrogen-bond in terms of the IR red-shift in the stretching frequency of the hydrogen-bond donor group. Herein, the strength of the S-H···S hydrogen-bond has been determined by measuring the red-shift (∼150 cm-1) of the S-H stretching frequency in a model complex of 2-chlorothiophenol and dimethyl sulfide using isolated gas-phase IR spectroscopy coupled with quantum chemistry calculations. The observation of an unusually large IR red-shift in the S-H···S hydrogen-bond is explained in terms of the presence of a significant amount of charge-transfer interactions in addition to the usual electrostatic interactions. The existence of ∼750 S-H···S interactions between the cysteine and methionine residues in 642 protein structures determined from an extensive Protein Data Bank analysis also indicates that this interaction is important for the structures of proteins.