A trifluoromethanesulfonate (OTf) and tert-butylacetylene (^tBuCC⁻) co-protected silver nanocluster (NC), Ag₄₃(^tBuCC)₂₄(CF₃SO₃)₈ (Ag₄₃), was synthesized and characterized. Single crystal X-ray diffraction analysis revealed its total structure. 43 Ag atoms are arranged into a three-concentric-shell Ag@Ag₁₂@Ag₃₀ structure. Both OTf and ^tBuCC⁻ ligands bonded with Ag atoms in a μ₃ mode. The application of Ag₄₃ as a catalyst for the reaction of silane with alcohol or H₂O indicated that the surface ligands had a profound passivation effect, which significantly influenced the reactivity and selectivity.