Background: Recently, emerging evidence has suggested the role of long non-coding RNAs (lncRNAs) in human carcinogenesis. Herein, we aimed to detect the expression profiles and functional implications of lncRNA GHET1 in human HCC. Methods: GHET1 levels in a cohort of 179 pairs of HCC tissues and pair-matched noncancerous hepatic tissues were tested using quantitative real-time PCR (qRT-PCR). The correlations of GHET1 expression with clinicopathologic features and prognostic outcomes were also analyzed in these HCC patients. The effects of GHET1 on HCC cell proliferation, cell-cycle profiles, Cyclin D1 expression and cell migration/invasion in vitro were investigated through CCK-8, flow cytometer, Western blot and transwell assays, respectively. Results: We verified that GHET1 was significantly up-regulated in HCC compared with corresponding non-tumor tissues, and a high level of GHET1 was correlated with larger tumor size, advanced TNM stage, and positive vascular invasion. HCC patients with high GHET1 expression level had shorter OS and DFS than the low GHET1 expression group, and multivariate logistic regression analysis considered high GHET1 expression as an independent factor of unsatisfactory prognosis. Functionally, knock-down of GHET1 attenuated HCC cell proliferation in vitro through inducing G0/G1 arrest and inhibiting Cyclin D1 expression. In addition, knock-down of GHET1 also inhibited migration and invasion ability of HCC cells in vitro. Conclusions: Collectively, these data demonstrated that GHET1 is obviously increased in HCC tissues, and uncontrolled GHET1 overexpression might drive HCC progression. Therefore, GHET1 might serve as a novel indicator of unsatisfactory prognosis and a promising therapeutic target for HCC patients.