Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, characterized by high mortality rate and poor prognosis. Our understanding of the HCC pathology is still very much fragmented and little progress has been made to improve the clinical outcome of HCC patients. While recently discovered microRNA deregulation in HCC has added to the complexity of our understanding of HCC, it has also presented promising novel approaches to understand, diagnose and treat HCC. Here, we highlight one miRNA, miR-224, which has been more consistently reported to be upregulated in HCC than other miRNAs. We will discuss the validated and predicted functional roles of this miRNA in HCC, speculate on the possible mechanism for its upregulation in HCC and explore the potential of miR-224 as an exciting novel biomarker for the early detection of liver malignancies as well as a novel therapeutic target for HCC treatment.