Alcohol consumption is a tradition in most cultures but are increasingly being arised as possessing a potential for misuse. Punicalagin is a phenolic compound that is found in forms alpha and beta in pomegranates. In this study, the protective role of punicalagin on oxidative stress, inflammation and DNA damage caused by ethanol (EtOH) in liver tissue were examined. Wistar albino rats were divided into 4 groups as control, eth, punicalagin, EtOH EtOH + punicalagin. In EtOH groups, rats were treated with EtOH (4g/kg) for 21 days, in punicalagin groups, rats were treated with punicalagin (4 mg/kg) for 21 days. In the liver tissue, superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) and glutathione (GSH) levels, in serum AST, ALT, LDH activities and TNF-α, IL-6 levels were measured. Genotoxicity was evaluated using comet assay. Based on these experimental results, while EtOH increased ALT, AST and LDH enzyme activies and induced inflammation and oxidative stress. Punicalagin reduced IL6, TNF-α, MDA levels, ALT, AST, LDH enzyme activities and increased SOD, CAT activities and GSH levels. EtOH significantly increased the percentage of damaged cells (type II, III and IV) and genetic damage index compared to the other groups (control, punicalagin and EtOH +punicalagin). Punicalagin was not genotoxic compared to the control. Furthermore, punicalagin reduced the genotoxic effect, induced by EtOH, with the sharp decrease in damaged cells (from 14.00±1.22 to 2.20±1.30) and genetic damage index (from 1.20±0.05 to 0.14±0.05). Punicalagin has antioxidant, antiinflammatory and protective role against to ethanol induced liver toxicity.