The maternally expressed gene 3 (MEG3) acts as an antitumor component in different cancer cells. However, MEG3 variant has been shown to confer cancer susceptibilityand certain polymorphisms within MEG3 are implicated in cancer risk (rs7158663, rs4081134, and rs11160608). Moreover, MEG3-TTCC and MEG3-CCCA promote the differentiation of SCs by activating the JAK2/STAT3 signaling pathway in different degrees. In particular, the alleles of MEG3 (AA, GA + AA) and MEG3 (rs7158663) were associated with an increased risk for human liver cancer. Moreover, Sirt2 is a specific NAD-dependent histone deacetylase for H4eK16 and has a strong preference for histone H4K16Ac in their deacetylation activity. Nevertheless, the functions and mechanism of MEG3 variant on hepatocarcinogenesis have not yet been well-demonstrated.