--- - |2+ Increasing evidence has shown that the lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) play important roles in cell proliferation, migration, and invasion in various tumors. In our current study, we concentrated on the biological mechanisms of NEAT1 in hepatocellular carcinoma (HCC) development. It was found that NEAT1 was significantly increased in human HCC cell lines including Hep3B, LM3, MHCC97L, SK‐hep1, and HepG2 cells compared to the normal human liver cell line LO2. Meanwhile, we observed that hsa‐miR‐139‐5p was greatly decreased in HCC cells, which suggested a negative correlation between NEAT1 and hsa‐mir‐139‐5p. In addition, NEAT1 downregulation can restrain HCC cell growth, migration, and invasion. Consistently, overexpression of hsa‐mir‐139‐5p exerted a similar phenomenon. Dual‐luciferase reporter assay, RIP assay, and RNA pull‐down assay confirmed that NEAT1 can function as a ceRNA by sponging hsa‐mir‐139‐5p. In addition, TGF‐β1 was identified as a downstream target of hsa‐mir‐139‐5p and hsa‐mir‐139‐5p overexpression was able to suppress TGF‐β1 levels. Furthermore, it was indicated that TGF‐β1 inhibition can inhibit HCC cell growth, migration, and invasion ability. Taken these together, we speculated that NEAT1 can modulate TGF‐β1 expression by sponging hsa‐mir‐139‐5p in HCC. These data indicates that targeting the NEAT1/hsa‐mir‐139‐5p/TGF‐β1 axis could be a new strategy for HCC. - Journal of Cellular Physiology, Volume 233, Issue 11, Page 8578-8587, November 2018.