Interestingly, the cancer cell killing activity of Ha2bm-d19 was increased by 54.4% under hypoxia, as compared to under normoxia, in AFP-negative HCC cells (HepI; P < 0.001), indicating that HREs can enable oncolytic Ads to target the hypoxic tumor microenvironment of HCC. This evidence concerns the gene AFP and hepatocellular carcinoma.