Hepatocellular carcinoma(HCC)is one of the most common cancers in the world.Surgical resection has been considered the optimal treatment approach,but onlya small proportion of patients are suitable candidates for surgery,and the relapserate is high.Approaches to prevent recurrence,including chemoemboliza-tionbefore and adjuvant therapy after surgery,have proven to have a limited benefit;liver transplantation is successful in treating limited-stage HCC because only aminority of patients qualify for transplantation.Therefore,new therapeutic strat-egies are urgently needed.Because in addition to the classical genetic mecha-nisms of deletion or inactivating point mutations,epigenetic alterations,such ashyperacetylation of the chromatin-associated histones(responsible for genesilencing),are believed to be involved in the development and progression ofHCC,novel compounds endowed with a histone deacetylase(HDAC)inhibitoryactivity are an attractive therapeutic approach.In particular,pre-clinical resultsobtained using HA-But,an HDAC inhibitor in which butyric acid residues areesterified to a hyaluronic acid backbone and characterized by a high affinity forthe membrane receptor CD44,indicated that this class of compounds may repre-sent a promising approach for hepatocellular carcinoma treatment. One of the most common cancers in the world. Surgical resection has been considered the optimal treatment approach, but only small proportions of patients are suitable candidates for surgery, and the relapserate is high. Approaches to prevent recurrence, including chemoemboliza-tionbefore and adjuvant therapy after surgery, have proven to have a limited benefit; liver transplantation is successful in treating limited-stage HCC because only aminority of patients qualify for transplantation.Therefore, new therapeutic strat-egies are urgently needed.Because in addition to the classical genetic mecha-nisms of deletion or inactivating point mutations, epigenetic alterations, such ashyperacetylation of the chromatin-associated histones (responsible for genesilencing), are believed to be involved in the development and progression ofHCC, novel compounds endowed with a histone deacetylase (HDAC) inhibitoryactivity are an attractive therapeutic approach.In particular, pre-clinic al resultsobtained using HA-But, an HDAC inhibitor in which butyric acid residues are esterified to a hyaluronic acid backbone and characterized by a high affinity forthe membrane receptor CD44, indicates that this class of compounds may repre-sent a promising approach for hepatocellular carcinoma treatment.