Cisplatin is one of the commonly used antitumor drugs for the treatment of different cancers. One of the mechanisms of cisplatin cytotoxicity is associated with oxidative stress initiation. Increased levels of the reactive oxygen species (ROS) are detected in many types of malignancies enhance the cells’ proliferative activity, but its excessively high levels can lead to apoptosis. Thus, one of the promising therapeutic strategies for cancer treatment is the regulation of intracellular ROS levels by targeted drugs. Physcion is an inhibitor of 6PGD enzyme which catalyzes the intracellular antioxidant NADPH formation (Lin et al. in Nature Cell Biology, 17 (11), 1484–1496, 2015 ). In this study, the combined action of the cisplatin and Physcion on the ROS level and viability of human lung (H1299) and pancreatic cancer cell lines (AsPC-1) is described. It was shown that the combined action of Physcion with cisplatin caused a growth in the ROS level in H1299 and AsPC-1 cells up to 1.7 and 2.5 times, respectively, compared with cisplatin alone. Moreover, IC50 of the cisplatin in combination with Physcion decreased up to 1.6 times in the AsPC-1 cells and up to 2.2 times in Н1299 cells compared with cisplatin alone. The enhancing effect of Physcion on cisplatin cytotoxicity is supposedly associated with a ROS balance shift toward increase. Physcion could be considered as an adjunct compound for cancer treatment with DNA-damaging agents.