BACKGROUND Recent evidence reveals that the inflammatory microenvironment is associated with tumor migration, invasion, and metastasis. Tumor necrosis factor-α (TNF-α) play a vital role in regulation of the inflammatory process in tumor development. Nuclear factor-kappa B (NF-κB) is one of the key transcription factors which regulate processes in tumor promotion. The aim of this study was to explore the role of NF-κB on the invasion and migration of oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS The IKKβ and p65 mRNA and protein levels were determined by quantitative RT-PCR and western blot. Wound scratch healing assays and transwell migration assays were used to evaluate the effect of TNF-α and BAY11-7082 on the migration of the OSCC cell lines (HN4, HN6, and CAL27). RESULTS We observed a significant increase of the expression level of IKKβ and p65 in OSCC cells from the experimental group at 24 h, 48 h, and 72 h after TNF-α stimulation. Invasion and metastasis of OSCC cells was obviously improved after the TNF-α stimulation. Invasion and metastasis ability of OSCC cells was inhibited in the suppression group, and no significant changes were observed in expression level of IKKβ and p65 after the use of BAY11-7082. CONCLUSIONS Our results suggest that TNF-α enhances the invasion and metastasis ability of OSCC cells via the NF-κB signaling pathway.