<p>Atomically precise palladium (Pd) clusters are emerging as versatile nanomaterials with applications in catalysis and biomedicine. This study explores the synthesis, structure evolution, and catalytic properties of Pd clusters stabilized by cyclohexanethiol (HSC₆H₁₁) ligands. Using electrospray ionization mass spectrometry (ESI–MS) and single-crystal X-ray diffraction (SXRD), structures of the Pd clusters ranging from Pd₄(SC₆H₁₁)₈ to Pd₁₈(SC₆H₁₁)₃₆ were determined. This analysis revealed a structure evolution from polygonal to elliptical geometries of the Pd_<i>n</i>S_2<i>n</i> frameworks as the cluster size increased. UV–Vis-NIR spectroscopy, combined with quantum chemical calculations, elucidated changes in the electronic structure of the clusters. Catalytic studies on the Sonogashira cross-coupling reactions demonstrated a size-dependent decline in activity attributed to variations in structural arrangements and electronic properties. Mechanistic insights proposed a distinctive Pd^(II)–Pd^(IV) catalytic cycle. This research underscores how ligands and cluster size influence the structures and properties of Pd clusters, offering valuable insights for the future design and application of Pd clusters in advanced catalysis and beyond.</p> Graphic abstract <p></p>