Here, we report a series of atomically precise Au 36 nanoclusters protected by thiol ligands to explore the influence of organic-inorganic interfaces, that is, the local environment around heterogeneous catalysts, on catalytic oxidation of CO. Our studies give molecular-level insights into the relationship between the catalytic reactivity and the metal-ligand surface bonding, which tunes access to the active sites, thereby precisely tailoring the activity of the Au 36 catalysts for CO oxidation.