ABSTRACT: Radiofrequency electromagnetic radiation (RF-EMR) of mobile phone has adverse effects on human health, such as the liver tissue. Melatonin, as a neurohormone has antioxidant property. The aim of present study was to evaluate the protective effects of melatonin on liver damage induced by mobile phone-radiofrequency radiation. Matherials and Methods: In this experimental study, 32 adult male BALB/c mice were divided randomly into four groups: control group (received only normal saline), melatonin group (2 mg/kg, for 30 consecutive days, intraperitoneally), Electromagnetic radiofrequency radiations (RF-EMR) group (4 hours per day for 30 consecutive days, whole body), and melatonin + RF-EMR) group (melatonin was prescribed one hour before exposure to RF-EMR. One day after treatment period were evaluated oxidative stress parameters, serum biochemical, and histopathological assays of liver. Results: The results exhibited that RF-EMR significantly increased oxidative stress (increased Malondialdehyde and decreased Glutathione level) compared with control and melatonin group (P < 0.001). Histopathological findings in the RF-EMR group showed periportal leucocyte infiltration, dilation of sinusoids, necrosis, vacuolation, and granulomatous formation. Also, alanine transaminase and aspartate transaminase, alkaline phosphatase in serum increased significantly compared with control and melatonin groups (P<0.001). Melatonin administration significantly reduced oxidative stress (P<0.01) in the radiated mice and ameliorated histopathological compared with control group. Conclusion: The data indicate that RF-EMR induces oxidative damage and changes histopathological structure in the liver. Melatonin decreased oxidative stress and improved the liver damage induced by RF-EMR.