Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths globally. Despite recent progress in development of HCC therapies, the median overall survival of advanced stage HCC patients is still only 12 months, which underscores the unmet medical need for novel therapeutic approaches for treatment of HCC. We aim to identify HCC-associated lncRNAs and circRNAs by RNA sequencing of HCC biopsies, uncover their molecular functions and evaluate the efficacy of design-optimized antisense oligonucleotide compounds targeting candidate lncRNAs in mouse models of HCC.