In order to explore potential mechanisms underlying protective effects of estrogen on HCC development, the comprehensive global transcriptome profiles regulated in response to E2, ERα specific agonist PPT, or ERβ specific agonist DPN were generated using RNA-Seq as an approach for genome-wide expression profiling and then analyzed by KEGG functional pathway enrichment analysis. The gene discussed is ESR2; the disease is hepatocellular carcinoma.