Macrocyclic molecules with multiple coordination sites have been widely used as promising ligands to build polynuclear metal clusters; however, cyclic silsesquioxane-based metal clusters are still rare. Herein, we report a new octanuclear Co-silsesquioxane cluster [Co-8(OH)(2){(MeSiO2)(6)}(2) (bpy)(2)(Obpy)(2)] (SD/Co8c; SD = SunDi), wherein the Co-8 disc-like core is sandwiched by two hexamethylcyclohex-asiloxanolate ligands (MeSiO2)(6) at two poles and finally encircled by two bpy (bpy 2,2'-bipyridine) and two Obpy (HObpy = 6-hydroxy-2,2'-bipyridine) ligands at the equatorial region. Interestingly, both MeSi(OMe)(3) and bpy undergo in situ transformations to generate hexameric cyclic (MeSiO2)(6) and Obpy, respectively. The unusual hydroxylation of bpy and the OH- anion in the center of Co-8 core provide additional binding sites to induce the formation of the larger cluster instead of the traditional hexanuclear cluster. The solution stability and fragmentation route in the gas phase were studied by cold-spray ionization and collision-induced dissociation mass spectrometry, respectively. Both results reveal that the Co-8 core is quite stable in solution as well as in the gas phase, even with increased collision voltage. Magnetic susceptibility studies of SD/Co8c show the slow magnetization relaxation indicative of single-molecule magnet (SMM) behavior. This work not only presents the multiple in situ ligand-transformation-assisted assembly of polynuclear cobalt cluster but also provides some new insights into the magnetism-structure relationship for SMMs.