Hepatocellular carcinoma is one of the most common highly malignant tumors in humans, as well as the leading cause of cancer-related death worldwide. Growing evidence has indicated that lncRNAs are implicated in different molecular mechanisms, including interactions with DNA, RNA, or protein, so that to regulate the gene expression at epigenetic, transcriptional, or posttranscriptional level. Moreover, the mechanism of action of lncRNA is closely related to its subcellular localization. An increasing number of studies have certified that lncRNA plays a significant biological function in the occurrence and development of hepatocellular carcinoma, such as involving in cell proliferation, metastasis, apoptosis, ferroptosis, autophagy, and reprogramming of energy metabolism. As a result, lncRNA has great potential as a novel biomarker for diagnosis or therapeutics of hepatocellular carcinoma. In this review, we highlight the correlation between subcellular localization of lncRNA and its mechanism of action, discuss the biological roles of lncRNA and the latest research advances in hepa-tocellular carcinoma, and emphasize the potential of lncRNA as a therapeutic target for advanced patients of hepatocellular carcinoma.