GHET1 expression was significantly up-regulated in HCC tissues and the higher level of GHET1 was related to vascular invasion, cirrhosis, tumor size, edmindson grade, and poor prognosis. Moreover, knockdown of GHET1 inhibited cell proliferation of HCC, and also caused cell cycle arrest and induced apoptosis in HCC cell lines. We also found that GHET1 could epigenetically repress transcription of Kruppel-like factor 2 (KLF2) in HCC cells by recruiting PRC2 into KLF2 promoter region. Our results indicated that lncRNA GHET1, as a growth regulator, might serve as a novel prognostic biomarker and therapy target for HCC. patients with high expression level of GHET1 had a significantly shorter overall survival than those with low expression level of GHET1.