AXIN2, an important regulator in Wnt/β-catenin signaling pathway, takes part in regulating cell proliferation, cytometaplasia, migration, apoptosis and other important functions, has showed close relations with the development of liver cancer, colon cancer, lung cancer, breast cancer and so on. The epigenetic regulation provides new insights for further exploring the pathogenesis of tumor. In this paper, the roles of AXIN2 in tumorigenesis, AXIN2 methylation, ubiquitination and siRNA/RNA regulation will be reviewed.