In the current study, we first identified novel hypoxia-driven genes between HCC tissues with high and low hypoxia signature, and used the novel hypoxia-driven genes (EGLN3, CHGA and CFHR3) to construct a risk model, and it showed remarkable prognostic effectiveness in HCC in both TCGA and ICGC cohorts. Here, EGLN3 is linked to hepatocellular carcinoma.