In conclusion, we report for the first time that a common variant of the TERT gene, rs2853669, is significantly associated with a high risk of death and cancer recurrence in patients with liver cancer, and that the rs2853669 variant (−245T > C), combined with the −124C > T mutation, mediates TERT transcriptional activity by modulating the binding of both E2F1 and ETS2, which is responsible for the high risk of HCC. This evidence concerns the gene ETS2 and hepatocellular carcinoma.