Objective: To investigate the roles and mechanisms of Raf kinase inhibitory protein (RKIP) in the invasion and metastasis of nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to detect the expression levels of RKIP in the NPC tissue specimens with different metastasis; Establishment of stable transfected NPC cell lines with RKIP expression changes using lipofectamine 2000; Scratch wound-wealing assay and traswell invasion assay were performed to determine the ability of cell migration and invasion; Western blot was used to detect the phosphorylated levels of NF-κB signaling molecules in NPC cells. Results: RKIP expression was significantly reduced in the NPCs relative to normal nasopharyngeal mucosa, and in the NPCs with metastasis relative to NPCs without metastasis, and there was not PKIP expression in the almost all lymphonode metastases. RKIP expression was found to be significantly associated with lymph node and distant metastasis, advanced clinical stage and reduced overall survival. Stable overexpression of RKIP in 5-8F NPC cells dramatically decreased tumor cell migration and invasion, whereas stable knockdown of RKIP in 6-10B NPC cells significantly increased tumor cell migration and invasion. RKIP expression levels were negatively associated with the activity of NF-κB signaling pathway, and Bay11-7082 could inhibit the migration and invasion of 6-10B cells with RKIP knockdown. Conclusion: RKIP may be a metastatic suppressor protein of NPC, NPC patients with low RKIP level had a poor prognosis, and RKIP downregulation promoted NPC invasion and metastasis by activating NF- κB signaling pathway.