Our recent data have shown that β-catenin drives a metabolism-directed transcription in the liver (Gougelet, Hepatology 2014), related to its role in liver zonation (Benhamouche, Dev Cell 2006). This transcription is aberrantly activated in liver cancers, together with the appearance of new oncogenic targets (Torre, J Hepatol 2011 ; Gougelet, Hepatology 2014). We have recently proposed a therapeutic strategy specific for β-catenin-activated liver cancers, based on miRNAs (Gougelet, Gut 2016). We search for the epigenetic hallmarks which regulate these transcriptional programs, and for the key targets responsible for liver carcinogenesis.