Purpose: To review the potential protective role of hydrogen against cisplatin-induced side effects during chemotherapy. Methods: We searched PubMed and SCOPUS using the following keywords and combinations in titles, keywords, abstracts and full texts: cisplatin; side effects; chemotherapy; tumor; toxicity; hydrogen; reactive oxidative species; and ischemic reperfusion. Results: The pathogenesis of cisplatin-induced side effects is suggested based on the increased level of reactive oxidative species (ROS). Cisplatin induces ROS-dependent platelet apoptosis via the extracellular signal-regulated kinase (ERK) signaling pathway, which might have contributed to cisplatininduced hematotoxicity, and in particular, thrombocytopenia. Molecular hydrogen has been shown to have therapeutic effects against damage to various organs (especially kidney, brain and liver) caused by ischemic reperfusion (IR) through selective elimination of the most cytotoxic ROS hydrogen radicals without affecting other types of ROS involved in signal transduction in vitro and in vivo. Conclusion: Hydrogen may not only alleviate hematotoxicity in patients with hemorrhagic tendencies during cisplatin-based chemotherapy, but also has a potential protective effect against other side effects induced by cisplatin.