Zearalenone is a mycotoxin widely found worldwide that is produced by several fungal species. Due to its similarity to estradiol, it has been shown to have toxic effects on the reproductive system. Although various animal studies have been conducted to investigate the toxic effects of zearalenone, the mechanisms of toxicity have not been fully elucidated. The aim of the study was to investigate the dose-dependent toxic effects of zearalenone exposure in human kidney cells. The half-maximal inhibitory concentration values of zearalenone in HK-2 cells were found to be 133.42 and 101.74 mu M in MTT- and NRU-tests, respectively. Zearalenone exposure at concentrations of 1, 10 and 50 mu M decreased cell proliferation by 2.1, 11.07 and 24.34%, respectively. Reactive oxygen species levels increased significantly in a dose-dependent manner. A significant increase was observed in the expressions of MGMT, alpha-GST, Hsp70 and HO-1 genes, which are associated with oxidative damage, while a significant decrease in L-Fabp gene expression was observed. Moreover, zearalenone increased gene expression of inflammatory cytokines, such as IL-6, IL-8, TIVF alpha and MAPK8. Significant increases were observed at the level of global DNA methylation and expression of DNMT1 in all exposure groups. These results indicate that changes in DNA methylation and oxidative damage may play an important role in the toxicity of zearalenone.