Aberrant expression of long non-coding RNAs (lncRNAs) has been observed in hepatocellular carcinoma (HCC) and confirmed to participate in the initiation and progression of HCC. In the present study, we identified a novel functional lncRNA, hedgehog-interacting protein antisense RNA 1 (HHIP-AS1). The expression levels of HHIP-AS1 were significantly decreased in HCC tissues. Downregulation of HHIP-AS1 expression correlated with larger tumor size, metastasis, and advanced TNM stage, and also predicted worse overall survival rate of HCC patients. Through performing overexpression and knockdown experiments, the biological function of HHIP-AS1 was identified to suppress HCC cell proliferation, migration and invasion, while promote apoptosis. Further investigation showed that HHIP-AS1 interacted with and positively regulated the stability of HHIP mRNA in a HuR-dependent manner. HHIP-AS1 exerted its suppressive effects through HHIP. Taken together, our findings demonstrate that HHIP-AS1 represses HCC progression by promoting HHIP expression, and indicate that the use of HHIP-AS1 may offer a promising treatment for HCC patients. Copyright © 2019 Elsevier Inc. All rights reserved.