In the present study, we therefore evaluated interactions between TRAIL and IER3 via co-immunoprecipitation and immunofluorescence analyses, leading us to determine that these two proteins were able to drive the apoptotic death of hepatocellular carcinoma (HCC) cells and to disrupt their proliferative and migratory abilities both in vitro and in vivo. This evidence concerns the gene TNFSF10 and hepatocellular carcinoma.