Four new octanudear Ru(II) cages (OC-1-OC-4) were synthesized from dinuclear p-cymene ruthenium(II) acceptors [Ru-2(mu-eta(4)-C2O4)(CH3OH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (A(1)), [Ru-2(mu-n(4)-C6H2O4)(CH3OH)(2)(eta(6)-p-cymene)(2)]-(O3SCF3)(2) (A(2)), [RU2(dhnq) (H2O)(2) (eta(6)-p-cymene)(2)] (O3SCF3)(2) (A(3)), and [Ru-2(dhtq)(H2O)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (A4) separately with a tetradentate pyridyl ligand (L-1) in methanol using coordination-driven self-assembly [L-1= N,N,N',N'-tetra(pyridin-4-yl)benzene-1,4-diamine]. The octanudear cages are fully characterized by various spectroscopic techniques including single-crystal X-ray diffraction analysis of OC-4. The self-assembled cages show strong in vitro anticancer activity against human lung adenocarcinoma A549 and human cervical cancer HeLa cell lines as observed from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Of all the octanuclear cages, OC-3 exhibits remarkable anticancer activity against both cancer cell lines and is more active than that reported for cisplatin. The excellent anticancer activity of OC-3 and OC-4 highlights the importance of the synergistic effects of the spacer component of the dinuclear p-cymene Ru(11) acceptor clips.