It is known that APE1/Ref-1 knockdown sensitizes cells to apoptosis induced by oxidative stress both in vitro [57] and in vivo [58], that APE1/Ref-1 silencing increases HCC sensitivity to radiotherapy by enhancing hepatocyte apoptosis, nevertheless the mechanism directly involved in APE1/Ref-1 apoptotic control is not well understood. This evidence concerns the gene APEX1 and hepatocellular carcinoma.