Hepatocellular carcinoma is the most common type of primary liver cancer, characterized by rapid progression, strong invasion, and diverse treatments. However, due to the large number of genes involved in its development and complicated mechanism, treatment resistance inevitably emerges, leading to ineffective therapeutic effects. Up to now the drug resistance mechanism has not been completely clarified. Long noncoding RNAs (lncRNAs) are a new class of noncoding RNAs with multiple biological functions, and may be involved in the development, transformation, and invasion of hepatocellular carcinoma through gene mutation, as well as in drug resistance by influencing the immune microenvironment of tumors and regulating the biological functions of tumor cells. In this paper, we reviewed the roles of lncRNAs in the chemotherapy, targeted therapy and immunotherapy resistance of hepatocellular carcinoma, hoping to provide new insight for drug resistance in hepatocellular carcinoma.