Changes to the epigenome are proposed to induce cell plasticity and alter the fitness of cancer cells.10 Various epigenetic regulators, including lysine methyltransferases (EZH2, SETDB1, and EHMT2), demethylases (KDM3A, KDM4B, KDM5B, and KDM1A), and deacetylases (SIRT7 and HDAC1–3) were shown to be frequently upregulated in HCC.11–13 Notably, mutations in epigenetic modifiers occur in about 50% of HCC cases, highlighting the need to identify chromatin regulators essential for HCC survival in order to develop new targeted therapies.14–20. This evidence concerns the gene KDM5B and hepatocellular carcinoma.