Hepatocellular carcinoma (HCC) is the leading cause of cancer-associated mortalities. The effective diagnostic and therapeutic targets for HCC are still unclear. miR-30e was differentially expressed in the majority of HCC tissues and cell lines. The aim of this study was to investigate the functional roles of miR-30e and their modulation of cancer networks in HCC cells. We determined the expression of miR-30e by quantitative real-time polymerase chain reaction, and found downregulation of miR-30e in HepG2 and HuH7 cells. miR-30e mimics significantly inhibited the proliferation, migration, and invasion of HepG2 and HuH7 cells, and promoted cell apoptosis, but did not influence the cell cycle. Dual-luciferase reporter assays were applied to identify JAK1 as target of miR-30e. miR-30e mimics downregulated the expression levels of JAK1 and vimentin in mRNA and protein in HepG2 and HuH7 cells. Silence of JAK1 by small interfering RNAs inhibited cell proliferation, migration and invasion of HCC cells. Furthermore, we verified that, IL-6, an agonist of JAK1/STAT3 pathway partly recovered the inhibition of miR-30e mimics on cell migration. Taken together, these findings confirmed our speculation that the functional effect of miR-30e on HCC cells, in part, is dependent on the JAK1/STAT3 signaling pathway. It was suggested that miR-30e has a critical role in the suppression of HCC and presents a novel mechanism of miRNA-mediated JAK1 expression in cancer cells that might be a good prognostic marker for survival of HCC patients.