Hepatocyte nuclear factor-4a (HNF4a) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis.There is striking suppression of hepatocellular carcinoma (HCC) by HNF4a, although the mechanisms by which HNF4a reverses HCC malignancy are largely unknown.Herein, we demonstrate that HNF4a administration to HCC cells resulted in elevated levels of 28 mature microRNAs (miRNAs) from the miR-379-656 cluster, which is located in the delta-like 1 homolog (DLK1)-iodothyronine deiodinase 3 (DIO3) locus on human chromosome 14q32.