Introduction: Ruthenium compounds are widely studied for its biological activity. However, potent ruthenium drugs often have limited bioavailability due to its poor aqueous solubility. In order to assist the preparation of these hydrophobic compounds, a carrier or drug delivery agent is often introduced. Herein, we encapsulated a hydrophobic ruthenium polypyridyl complex [Ru(dppz)PIP]2+, (dppz = dipyrido-[3,2-a:20,30-c]phenazine, PIP = 2-phenylimidazo[4,5-f][1,10] phenanthroline) in mesoporous silica nanoparticles (MSN). Methods: The MSN was synthesized by using ionic liquid 1-hexadecylphenanthrolinium as a novel template and have 833.99 m2/g in surface area. The cytotoxicity of the synthesized ruthenium complex, MSN and MSN-loaded ruthenium was studied on Hela and A549 cancer cell lines. Results: MSN was non-toxic at lower dosage (<500 µg) while [Ru(dppz)PIP]2+ displayed moderate toxicity against both cell lines, with IC50 of 17.27 µM and 19.92 µM for A549 and Hela, respectively. Remarkably, the encapsulated drug delivered higher toxicity at smaller concentration, with IC50 of 2.97 µM and 1.38 µM towards A549 and Hela, respectively. The results signify that [Ru(dppz)PIP]2+ potential in anti-cancer improved following encapsulation with MSN. Conclusion: This study indicates that mesoporous silica nanoparticles might be a useful drug delivery agent in promoting the bioavailability of hydrophobic ruthenium compound for biological activity.