Proton transfers are involved in many chemical processes in solution and in biological systems. Although water molecules have been known to transiently facilitate proton transfers, the possibility that water molecules may serve as the “storage site” for proton in biological systems has only been raised in recent years. To characterize the structural and possibly the dynamic nature of these protonated water clusters, it is important to use effective computational techniques to properly interpret experimental spectroscopic measurements of condensed phase systems. Bearing this goal in mind, we systematically benchmark the self-consistent-charge density-functional tight-binding SCC-DFTB method for the description of vibrational spectra of protonated water clusters in the gas phase, which became available only recently with infrared multiphoton photodissociation and infrared predissociation spectroscopic experiments. It is found that SCC-DFTB qualitatively reproduces the important features in the vibrational spectra of protonated water clusters, especially concerning the characteristic signatures of clusters of various sizes. In agreement with recent ab initio molecular dynamics studies, it is found that dynamical effects play an important role in determining the vibrational properties of these water clusters. Considering computational efficiency, these benchmark calculations suggest that the SCC-DFTB/molecular mechanical approach can be an effective tool for probing the structural and dynamic features of protonated water molecules in biomolecular systems.