Background/Aim: Cisplatin is a highly effective chemotherapeutic agent that is used to treat solid tumors; however, its severe side effects remain a limitation. In particular, the high incidence of cisplatin-induced ototoxicity has attracted interest. Melatonin has been shown to decrease the toxic effects of cisplatin due to its antioxidant activity, and could increase the efficacy of cancer chemotherapy. The aim of this study was to determine the effect of melatonin against ototoxicity in rats treated with cisplatin. Materials and Methods: Rats were randomly divided into four groups (saline, melatonin, cisplatin+saline, and melatonin+cisplatin). Distortion-product otoacoustic emission (DPOAE) measurements were carried out on days 1 and 8. Results: There was a decrease in DPOAE amplitudes in the animals that received cisplatin (10 mg/kg); however, the group treated with cisplatin+melatonin presented DPOAE amplitudes comparable to those of the control groups. Conclusion: Melatonin can be used as an adjuvant tumor treatment due to its ability to decrease cisplatin-induced ototoxicity.Cancer is currently a leading cause of death in both economically developed and less developed countries (1). Moreover, the global trend toward a shift in lifestyle habits that are known to increase the risk of cancer in less economically developed countries, comprising 82% of the world's population, is expected to lead to an increase in the number of new cancer cases in the next few years along with population growth and aging (1).Cancer chemotherapy was introduced in the 1940s when nitrogen mustard was first used in clinical practice. In 1969, Rosenberg et al. (2) first demonstrated the cytotoxic effect of cisplatin, and a new class of antitumor agents emerged (2). Although additional platinum analogues are clinically applied, cisplatin is still considered the most useful of these agents based on its versatility, long research history, and supportive literature (3). Indeed, cisplatin remains a highly effective chemotherapeutic agent that is widely used to treat solid tumors, including tumors of the ovary, testis, bladder, lung, and head and neck (4-6). In particular, cisplatin is one of the most effective chemotherapeutic agents for pediatric cancer patients, with an average cure rate of 85% (7, 8).The mechanism of cisplatin's antitumor activity essentially involves the binding of the drug to DNA and non-DNA targets. The damage induced by the binding of cisplatin to DNA inhibits DNA replication mechanisms, leading to cell death through apoptosis and necrosis of tumor cells (9).In clinical practice, the dose of cisplatin may be limited owing to its toxic side-effects such as nephrotoxicity, genotoxicity, neurotoxicity, and ototoxicity, often leading to a worse prognosis. Moreover, cancer patients, especially children, have a higher incidence of development of secondary tumors after cisplatin-based treatments, particularly in the proliferative organs. This is due to the genotoxic effects of the drug, which can affect all types of cell...