The interaction and H/D exchange of free and hydrogen-bonded Bro̷ nsted acid sites (BAS) of zeolite ZSM-5 (Si/Al = 14) with n-hexane were investigated by 1 H MAS NMR spectroscopy and DFT cluster model calculations. Three model sites were selected from the greater variety of possible BAS locations for model calculations to represent free BAS (Al12-O26(H)-Si12, site I) and strong (Al2-O7(H)-Si6, site II) or weakly hydrogen-bonded (Al5-O12(H)-Si4, site III) BAS. The molecule interacts with the BAS via van der Waals and Coulomb interactions. Strong hydrogen bonds of site II in 5-rings remain intact after n-hexane adsorption, whereas a rupture of weak hydrogen bonds of site III in 6-rings occurred. H/D exchange of the BAS with n-hexane is found for sites I and II at 423 K, but site III is not reactive at this temperature, indicating that the reactivity does not correlate with hydrogen bond strength. This is, at least to some extent, due to the strong adsorption of n-hexane in the groove of the zigzag channel of ZSM-5 for site III. These results contribute to deeper insights into hydrocarbon reactions with zeolite catalysts.