Long noncoding RNAs (lncRNAs) have been acknowledged as vital regulators in tumorigenesis of human cancers, including hepatocellular carcinoma (HCC). LINC00461 has been found to promote progression of glioma and breast cancer. Nevertheless, the function of LINC00461 in HCC is still unknown. Here, we found that LINC00461 was upregulated in HCC tissues and positively correlated with advanced stage and metastasis. Furthermore, LINC00461 overexpression in HCC patients predicts unfavorable prognosis. Loss-of-function assays showed that LINC00461 silencing suppressed the proliferation, migration and invasion of HCC cells in vitro, and impeded tumor growth in vivo. Mechanistically, LINC00461 inversely regulates miR-149-5p abundance in HCC. Further investigation indicated that LINC00461 was a competing endogenous RNA (ceRNA) by directly sponging miR-149-5p in HCC cells. Moreover, LRIG2 was identified as the downstream target of miR-149-5p and its expression was regulated by LINC00461/miR149-5p axis. Restoration of LRIG2 reversed LINC00461 knockdown attenuated HCC cell proliferation, migration and invasion. In summary, our findings revealed that LINC00461 is an oncogene in HCC through regulating miR-149-5p/LRIG2 pathway. (C) 2019 Elsevier Inc. All rights reserved.