Alcohol and its metabolite, acetaldehyde, mainly disrupt intestinal integrity by down-regulation of intestinal epithelial tight junction proteins. OFO exacerbates intestinal dysbiosis, particularly the overgrowth of bacteria Proteobacteria, leading to the increased bacterial endotoxin. The impaired intestinal barrier facilitates endotoxin translocation from the intestinal lumen into the portal circulation. Subsequently, the gut-derived endotoxin activates hepatic Kupffer cells by TLR4-mediated NF-κB signaling pathway, resulting in hepatic inflammation, which induces hepatocyte damage. In summary, OFO exacerbates alcoholic liver injury via enhancing intestinal dysbiosis, barrier dysfunction and hepatic inflammation mediated by gut-derived endotoxin in mice. NF-κB nuclear factor κB, TLR4 Toll-like receptor 4, OFO Oxidized fish oil.