Introduction: Combination therapy to treat cancer have been demanded due to the complexity of the disease and to prevent resistance mechanisms commonly found in classic chemotherapeutic methods. Recently, we have reported that [Ru(dppz)2(PIP)]2+ (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) (RuPIP) immediately stalls replication fork progression in HeLa human cervical cancer cells. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells. These discoveries indicate that this class of compounds merit further investigation as anticancer drugs, especially within combinational therapy roles. However, information pertaining to the effects of combining ruthenium compounds with existing chemotherapeutic drugs remain scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using RuPIP in combination with cisplatin on different cancer cell lines. Methods: A549, MCF7, Hela and T24 cells were treated with different concentrations of RuPIP or cisplatin alone, as well as different combinations of these two agents at a fixed ratio 1:1 over the course of 72 hr to assess their individual and combination effects. Cell viability was analysed using MTT assay. The combination index (CI) was calculated based on the Chou Talalay Method. Results: Single-agent treatment at 72 hr with RuPIP or cisplatin led to dose-dependent decreases in the viability of the A549, MCF7, Hela and T24 cells at 72 hr. Furthermore, increasing the concentrations of the combinations up to four folds of half maximal inhibitory concentration (IC50) statistically decrease the cell survival rates of A549 and MCF7 cells thus, displayed synergistic effects. Conclusion: Treatment of MCF7 and A549 cells with a combination of RuPIP and cisplatin showed a synergistic effect and thus are promising as a combination therapy for cancer treatment.