Background: The aim of this study was to investigate hepatic lesions induced by the 2.45 GHz electromagnetic radiation (EMR) of Wi-Fi and the protective effects of Vitamin C (Vit C) in rats. Materials and Methods: Eighteen Sprague-Dawley female rats were randomly distributed into three groups, each containing six rats. The groups were Control, EMR (EMR, 1 h/day for 30 days) and EMR + Vit C (EMR, 1 h/day for 30 days and Vit C, 250 mg/kg/daily). At the end of the study, blood and liver tissue samples were collected for laboratory examinations. Results: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were increased in the EMR group compared with the control group. Liver histology of rats in the EMR group revealed severe hyperemia, slight degeneration, and lipidosis. Caspase-3, hypoxia-inducible factor-1 (HIF-1), and HIF-2 immunoexpression was increased, and Sirtuin-1 (SIRT-1) expression was markedly decreased in hepatocytes in the EMR group. Vit C treatment ameliorated both biochemical and pathological findings. Conclusion: The results of this study showed that 2.45 GHz (Wi-Fi) EMR can cause liver damage in rats, but Vit C has an ameliorative effect.