Long non-coding RNAs (lncRNAs) are classified as RNAs greater than 200 nucleotides in length without protein coding capability, which exert multiple functions upon a wide range of biological processes. Highly upregulated in liver cancer (HULC) is an lncRNA that was found specifically overexpressed in hepatocellular carcinoma (HCC). Recent evidence has indicated that lncRNA HULC is closely related to HCC and other HCC-related diseases (such as viral hepatitis and posthepatitic cirrhosis), involving in the occurrence and development as well as prognosis of HCC by multiple mechanisms such as epigenetic regulation, abnormal lipid metabolism, and promotiing angiogenesis and epithelial-mesenchymal transition. Moreover, lncRNA HULC has a potential value of acting as a diagnostic biomarker or therapeutic target for HCC. Here, the authors review the research progress in relationship between lncRNA HULC and HCC.