To understand the potential molecular mechanisms of estrogen and ERs in HCC, RNA sequencing (RNA-Seq) was used to generate comprehensive global transcriptome profiles of HepG2, the most commonly studied human HCC cell line, following treatment of vehicle (control), estradiol (E2), ERα-specific agonist PPT, or ERβ-specific agonist DPN. Here, ESR1 is linked to hepatocellular carcinoma.