Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. HCC is characterized by a poor prognosis and an ever increasing number of scientific studies aim to find new diagnostic, prognostic, and therapeutic targets. MicroRNAs (miRNAs), small non-coding RNAs that regulate the gene expression in many processes, have been shown to play a crucial role in regulating hepatocellular carcinoma. miRNAs may act as oncogenic miRNAs and tumor suppressor miRNAs and regulate cancer cell proliferation, invasion, and metastasis by being differently upregulated or downregulated and targeting the genes related with carcinogenesis. miRNAs secreted from cancer cells are found circulating in the blood, presenting an opportunity for their use as disease-related biomarkers. Moreover, extracellular vesicle-derived miRNAs are known to reflect the cell of origin and function and may provide effective biomarkers for predicting diagnosis and prognosis and new therapeutic target in HCC. In this article, we describe the most recent findings regarding the molecular mechanisms and gene regulation of microRNA in HCC, as well as their application in diagnosis/prognosis and treatment.