and mRNA but does not stabilize EGFR mRNA. Thus the effects of LMP1 are likely to be mediated by direct activation of the EGFR promoter. In this study, induction of LMP1 increased the EGFR in both protein and promoter levels in a dose dependent 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 NF_B activation by constitutive repressive inhibitory kappa B alpha (I_B_) marginally decreased EGFR promoter activity using transiently transfected I_B_ dominant negative mutant. Promoter mutagenesis analysis demonstrated that two putative NF_B binding sites of EGFR promoter were very necessary for the transcriptional activity of EGFR induced by LMP1, the proximal NF_B binding site was more important than the distal NF_B binding site. Taken together, Epstein–Barr virus latent membrane protein 1 modulated the EGFR promoter activity in a NF_B dependent manner.