The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) oncoprotein may cause multiple cellular changes including the induction of epidermal growth factor receptor (EGFR) expression and activation of the NFnB transcription factor. LMP1 increases the levels of both EGFR protein and mRNA, but does not stabilize EGFR mRNA. Thus, the effects of LMP1 are likely to be mediated by the direct activation of the EGFR promoter. In this study, induction of LMP1 increased the EGFR in both protein and promoter levels in a dosedependent manner using tetracycline-regulated LMP1 expression in nasopharyngeal carcinoma (NPC) cell line. Mutational analysis of the LMP1 protein indicated that the C-terminal activation region-1 (CTAR1) domain was mainly involved in the EGFR promoter induction, while CTAR2 was necessary but not sufficient to induce EGFR promoter. Inhibition of LMP1-mediated NFnB activation by constitutive repressive InBa marginally decreased EGFR promoter activity using transiently transfected InBa dominant negative mutant. Promoter mutagenesis analysis demonstrated that two putative NFnB binding sites of EGFR promoter were very necessary for the transcriptional activity of EGFR induced by LMP1, the proximal NFnB binding site was more important than the distal NFnB binding site, and both NFnB binding sites played a cooperative role. Taken together, Epstein-Barr virus latent membrane protein 1 modulated the EGFR promoter activity in a NFnB-dependent manner.