Understanding the isomerism phenomenon at the nanoscale is a challenging task because of the prerequisites of precise composition and structural information on nanoparticles. Herein, we report the ligand-induced, thermally reversible isomerization between two thiolate-protected 28-gold-atom nanoclusters, i.e. Au-28(S-c-C6H11)(20) (where -c-C6H11 = cyclohexyl) and Au-28(SPh-Bu-t)(20) (where -Ph-Bu-t = 4-tert-butylphenyl). The intriguing ligand effect in dictating the stability of the two Au-28(SR)(20) structures is further investigated via dispersion-corrected density functional theory calculations.