Taken together, we integrated the expression matrix of ER-related genes and clinical traits within both TCGA-LIHC and GSE14520 cohorts to develop and validate a novel ER-associated clinical prognostic model of HCC patients, which contains the combined panel of five hub genes (KPNA2, FMO3, SPP1, KIF2C, and LPCAT1). Here, FMO3 is linked to hepatocellular carcinoma.