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. The gene discussed is E2F1; the disease is hepatocellular carcinoma.