Chemotherapeutics in cancer treatment have a wide range of non-specific effects, there is an urgent need to develop safety and cost effective drugs [1]. In this context, a number of Schiff base ligands bearing 1,3-diaminobenzene backbone (1-5) and their PdII (6-10) and RuII (11-15) derivative complexes were synthesized from 1,3-diaminobenzene, Ar-aldehydes (Ar-BzH) (4methylBzH (1), 4-methoxyBzH (2), 4-nitroBzH (3), 4-chloroBzH (4) and 3,4,5-trimethoxyBzH(5)), PdCl2 and [RuCl2(p-cymene)]2, respectively. These compounds were characterized by various methodologies including 1H and13C-NMR, thermal analysis (TG/DTA), FT-IR, elemental analysis (E.A.) and tested for their in vitro anti-proliferative activities against A549 (human lung adenocarcinoma) and Colo-205 (human colon carcinoma) cell line. Moreover, cytotoxic RuII complexes were selected (11, 13 and 15) and to explore the underlying molecular mechanisms involved in cell death process. All the compounds have not been remarkable cytotoxic effect on Colo-205 cells. The compounds (1-5) and their PdII complexes (6-10) were not effect on A549 cell viability, but the RuII complexes (11, 13 and 15) were able to markedly inhibit cell growth. Further investigation on intracellular mechanisms revealed that, treatment with compounds 11, 13 and 15triggered apoptosis by transcriptionally upregulate pro-apoptotic caspase 9 and caspase 3 levels in A549 cells. These findings suggest that some RuII complexes11, 13 and 15exhibits high cytotoxicity and induced apoptosis by induced caspase9/caspase3 genes and may contribute to the future development of improved chemo-therapeutics against human cancers.