Objective: Hepatocellular carcinoma (HCC) is a lethal malignancy in the world. LncRNA THUMPD3-AS1 is implicated in tumorigenesis and progression in various tumors. Therefore, this study was applied to investigate the action of THUMPD3-AS1 in HCC by regulating microRNA (miR)-4465 and KPNA2. Methods: The clinical specimens of HCC were collected to determine THUMPD3-AS1, KPNA2, miR-4465, E-cadherin, Vimentin, N-cadherin, ZEB1 and SNAIL levels. HCC cells were screened and transfected with sh-THUMPD3-AS1 or miR-4465 mimic to explore their roles in HCC cell phenotype and epithelial-mesenchymal transition (EMT)-related factors. The involvement of miR-4465 in THUMPD3-AS1-mediated HCC was proved. The relationship of THUMPD3-AS1, KPNA2 and miR-4465 was verified. Results: Overexpressed THUMPD3-AS1 and KPNA2 and reduced miR-4465 were present in HCC clinical tissues. THUMPD3-AS1 bound to miR-4465 to target KPNA2. Silencing of THUMPD3-AS1 or restoration of miR-4465 repressed HCC cell phenotypes and EMT in vitro. Inhibition of miR-4465 mitigated the role of silenced THUMPD3-AS1 in HCC. Conclusion: This study stresses that THUMPD3-AS1 induces EMT in HCC cells and ultimately promotes HCC cell growth and migration by competitively inhibiting miR-4465 expression and thus upregulating KPNA2.