Background: LncRNA has been shown to associates with the initiation and progression of hepatocellular carcinoma (HCC). Recently, some studies showed that HANR function as an oncogene in HCC; however, the detailed mechanism of HANR-regulated HCC tumorigenesis and progression needs to be elucidated. Methods: We used RT-qPCR method to probe genes expression. MTT assay, wound healing assay and transwell invasion assay were utilized to examine proliferation and migration and invasion abilities of HepG2 cells. Xenograft tumor experiment was used to show the growth of tumors in vivo. Results: HANR was evidently upregulated in HCC tumors and cells compared to normal tissues and cells. Besides, HANR knockdown induces attenuated cell proliferation, migration, invasion of HCC cells. By bioinformatic analysis and dual luciferase reporter assay, we found that miR-214 was the downstream target of HANR. Furthermore, miR-214 inhibitor largely enhanced tumor phenotypes of HCC cells regulated by HANR knockdown. HANR and miR-214 regulated the EZH2, then affecting TGFBR2 level. Finally, we demonstrated that EZH2 overexpression could greatly rescue HANR knockdown or miR-214 mimic-induced HCC tumorigenesis and progression. Conclusions: In this study, we report a newly identified regulatory mechanism HANR/miR-214/EZH2/TGF-beta axis, which is implicated in tumorigenesis and progression of HCC. Our findings suggest that HANR facilitates the development of therapeutical strategies or diagnostic markers by targeting HANR. (C) 2018 Elsevier Inc. All rights reserved.