Long noncoding RNAs (lncRNAs) were dysregulated in many kinds of cancers, including hepatocellular carcinoma (HCC). AK021443, as a novel lncRNA, was found to be upregulated in HCC, while its potential value and function are still unknown. The pathological changes of liver tissues were observed by hematoxylin and eosin staining. The expression levels of AK021443 in HCC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation ability of AK021443 on HepG2 and Bel-7402 cells was assessed by CCK8 and EdU staining assays. The role of AK021443 in HepG2 and Bel-7402 cell invasion and migration was measured by Transwell and wound healing assays. Finally, the expression of epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, vimentin, and snail, was investigated by qRT-PCR, Western blot, and immunofluorescence. The role of AK021443in vivo was also analyzed. Hepatoma cell nucleus increased in HCC tissues compared with normal liver tissues. AK021443 expression was increased in HCC tissues and cell lines. Knockdown of AK021443 significantly reduced HepG2 and Bel-7402 cell proliferation, invasion, and migration. Furthermore, inhibition of AK021443 in HepG2 and Bel-7402 cells significantly repressed EMT ability. Knockdown of AK021443in vivo also significantly inhibited tumor growth with decreased Ki-67 levels and EMT phenotype in tumor tissues. However, these functions could be reversed by overexpression of AK021443. AK021443 significantly controlled HepG2 and Bel-7402 cell proliferation, colony formation, invasion, and migration by repressing EMT, which might provide a potential therapeutic target for HCC diagnosis.