There is growing evidence that liver graft ischemia-reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence, but the involved mechanisms are unclear. Here, we tested the hypothesis that mesenteric congestion due to portal blood flow interruption induces endotoxin-mediated Toll-Like Receptor 4 (Tlr4) engagement, resulting in elevated liver cancer burden. We also assessed the role of remote ischemic preconditioning (RIPC) in this context.