In this work, the effects of thiolate ligands (-SR, e.g., chain length and functional moiety) on the accessibility and catalytic activity of thiolate-protected gold nanoclusters (e.g., Au-25(SR)(18)) for 4-nitrophenol hydrogenation is reported. The data suggest that Au-25(SR)(18) bearing a shorter alkyl chain shows a better accessibility to the substrates (shown by shorter induction time, t(0)) and a higher catalytic activity (shown by higher apparent reaction rate constant, k(app)). The functional moiety of the ligands is another determinant factor, which clearly suggests that ligand engineering of Au-25(SR)(18) would be an efficient platform for fine-tuning its catalytic properties.