Abstract: Objective To explore the role of Long noncoding RNA UFC1 (lincRNA-UFC1) in modulating the metastasis and invasion of hepatocellular carcinoma (HCC) cells and the underlying mechanism. Methods Human HCC cell line Huh7 was infected with the lentiviral vector carrying lincRNA-UFC1 to obtain a cell line with lincRNA-UFC1 overexpression. A short hairpin RNA (shRNA) targeting lincRNA-UFC1 was delivered in human HCC BEL-7402 cells via a lentiviral vector to obtain a cell line with lincRNA-UFC1 knockdown. Expression levels of lincRNA-UFC1 in the two HCC cell lines were detected using real-time PCR, and the changes in the cell invasion and migration in response to lincRNA-UFC1 overexpression or knockdown were analyzed using Transwell and wound-healing assays. The expressions of GSK-3β/β-catenin-related proteins in the cells were detected with Western blotting. XAV-939, a GSK-3β/β-catenin inhibitor, was used for assessing the impact of lincRNAUFC1 overexpression on the invasion and migration of the HCC cells through Transwell and wound-healing assays. Results Overexpression of lincRNA-UFC1 significantly promoted the invasion and migration of Huh7 cells as compared with the control cells (P<0.001), while lincRNA-UFC1 knockdown obviously suppressed the invasion and migration of BEL-7402 cells (P<0.001). The results of Western blotting showed that the expressions of proteins associated with the cell invasion and migration, namely β-catenin and P-GSK-3β, were significantly upregulated in response to lincRNA-UFC1 overexpression, and were obviously lowered after lincRNA-UFC1 knockdown. Treatment of the cells with XAV-939 significantly reversed the effect of lincRNA-UFC1 overexpression on the cell invasion and migration (P<0.001). Conclusion lincRNA-UFC1 overexpresison promotes cell invasion and migration through the GSK-3β/β-catenin axis in HCC cells in vitro.