Objective To investigate the role of tumor necrosis factor-α (TNF-α) in epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells and the related mechanism. Methods HCC cell lines Hep3B and SMMC-7721 were treated with TNF-α for 24 h; then the cell morphological changes were observed by microscope and the expressions of the epithelial markers (E-cadherin and β-catenin), mesenchymal markers (Vimentin and N-cadherin), and EMT associated transcriptional factor Twist were examined by RT-PCR and Western blotting analysis. The invasion and metastasis ability was evaluated by Transwell and wound healing assay. Luciferase reporter assay and immunofluorescence were used to determine NF-κB transcriptional activity; Western blotting analysis was used to examine the expression levels of IκBα and p-IκBα protien. Cells was also incubated with TNF-α and NF-κB inhibitor (BAY11-7082) together, and then the phenotype of EMT was detected by microscope, RT-PCR and Western blotting analysis. Results Hep3B and SMMC-7721 cells had EMT phenotype after treated with TNF-α. Wound healing assay showed that the wound healing rate of cells exposed to TNF-α was significantly increased compared with the non-treated group (P<0.05), and Transwell assay showed that more cells penetrating the membrane after treatment with TNF-α (P<0.05). TNF-α effectively promoted IκBα phosphorylation and the subsequent NF-κB nuclear translocation. We also found that TNF-α-mediated EMT could be converted by NF-κB inhibitor (BAY11-7082) (P<0.05). Conclusion TNF-α induces EMT of HCC cells through NF-κB-dependent pathways, and subsequently promotes the invasion and metastasis of HCC.