The incidence of hepatocellular carcinoma (HCC) is significantly lower in women than men, implying that estrogen receptors (ERs) may play an important role in this sex dimorphism. Recently, considerable progress has been made in expanding our understanding of the mechanisms of ERs in HCC. As one of the most important ERs, ERα functions as a tumor suppressor in the progression of HCC through various pathways, such as STAT3 signaling pathways, lipid metabolism-related signaling pathways, and non-coding RNAs. However, the function of ERα was reduced with the changes of some molecules in the liver, which may develop further into HCC and make it difficult to achieve an effective hormone treatment effect. Intriguingly, there are signs that individualized hormone therapy according to the activity of ERα will overcome this challenge. Based on these observations, it is particularly imperative to reassess and extend the function of ERα. In this review, we mainly elucidated molecular mechanisms associated with ERα in HCC and investigated the individualized hormone therapy based on these mechanisms, with the aim of providing new insights for HCC treatment.
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