Poncirin (PO) is a citrus flavonoid with various of functional effect including cardiac ischemia-reperfusion injury, colitis, cancer, et al. Considering the role of PO in improving inflammation and lipid metabolism, it may have potential therapeutic effects on alcoholic liver injury (ALI), but there are currently no relevant reports.Current study aimed to explore the protective effect of PO on preventing ALI.A chronic ethanol-fed mice was used as ALI-mice model and ethanol-induced mouse primary hepatocytes (MPHs) as ALI-cells model. Multiple molecular biology analysis methods are used to evaluate PO's efficacy.Both in vivo and in vitro, PO improved the inflammatory response and lipid deposition induced by ethanol. According to RNA-seq analysis, Peroxisome proliferator activated receptor alpha (PPARα) had been found as a potential target, followed by the experiment validation using Cellular Thermal Shift Assay (CETSA), Western bolt analysis as well as qPCR analysis. In addition, the protective effect of PO was reduced or disappeared in PPARα-/- ALI mice, both in vivo and in vitro.This is the first study to evaluate the role of PO in preventing ALI by targeting lipid metabolism and the inflammatory response by partly targeting the PPARα pathway, providing a fundamental basis for the use of PO as a functional food to alleviate ALI.