Here, we would demonstrate the effect of Nrf2 down-regulation on invasion, metastasis, and angiogenesis of HCC in vivo and in vitro by single administration of epirubicin (EPI, a common chemotherapeutic drug) and combined administration of EPI and CPT, aiming to provide a novel strategy for HCC treatment. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.