BACKGROUND: Liver ischemia-reperfusion injury (IRI) is a common complication of diseases such as liver transplantation, hepatic resection, and hemorrhagic shock. This study aimed to elucidate the molecular mechanism of miR-107 affecting hepatic ischemia-reperfusion injury (IRI). METHODS: The expression changes of miR-107 during hepatic IRI were quantified using quantitative real-time PCR. Subsequently, in vitro cellular experiments were carried out to verify the role of miR-107 on hypoxia/reoxygenation (HR) through CCK-8, flow cytometer, and commercial kits. In terms of mechanism, it was determined that miR-107 had a regulatory relationship with target genes through luciferase reporter assay. RESULTS: In mouse liver IRI, miR-107 expression was increased while HMOX1 expression was decreased in liver tissues. In vitro cellular experiments, miR-107 inhibitors favored the alleviation of proliferation, apoptosis, inflammation, and oxidative stress in HR-damaged liver sinusoidal endothelial cells. In the molecular mechanism study, we determined that miR-107 could bind to HMOX1 and inhibit the HMOX1 expression. Low HMOX1 expression could eliminate the protective effect of miR-107 inhibitors. CONCLUSION: MiR-107 expression was elevated during hepatic IRI and exacerbates hepatic injury by targeting HMOX1 inhibition.