Hepatocyte nuclear factors play the key role in the establishing and maintenance of hepatocyte differentiation. They not only control the expression of functional hepatic genes but are also involved in the regulation of proliferation, morphogenesis and detoxication in the liver. In this review we consider the main biological properties of the central regulator of hepatic differentiation HNF4alpha, patterns of its expression in embryogenesis and different adult tissues, mechanisms of regulation of its activity and transcriptional properties, and the essential target genes. Based on the studies of gene expression on the experimental models of rodent carcinogenesis and clinical samples of human liver tumors, the clear association of HNF4alpha transcriptional repression with progression and dedifferentiation of this type of tumors was shown. The possibility of the reversion of dedifferentiated hepatocarcinoma malignant phenotype by means of HNF4alpha exogenous expression confirms the important role of this factor in the coordination of proliferation, differentiation and the maintenance of epithelial morphology in several types of epithelial cells.