In this work, we describe two synthetic procedures for preparing palladium doped 25-atom nanoclusters (referred to as Pd1Au24(SR)18, where ―SR represents thiolate, R=C2H4Ph). Pure Pd1Au24(SC2H4Ph)18 nanoclusters are isolated by solvent extraction and size exclusion chromatography. Mass spectrometry and optical spectroscopy analyses demonstrate that the Pd1Au24(SC2H4Ph)18 nanocluster adopts the same core-shell structure as that of the homogold Au25(SC2H4Ph)18 nanocluster, that is, a Pd- or Au-centered icosahedron surrounded by six Au2(SR)3 “staple”-like motifs. Similar doping behavior has also been observed in 38-atom M38(SR)24 (M: metal) nanoclusters, indicating the unique behavior of Pd dopant being preferentially located in the icosahedral center. The catalytic activity of Pd1Au24(SC2H4Ph)18 has also been evaluated for the selective hydrogenation of α,β-unsaturated ketone (e.g., benzalacetone) to α,β- unsaturated alcohol, and a 42% conversion of benzalacetone is attained.