We provided cellular and clinical evidence revealing a close correlation among LMP1 expression, DNMT3b expression, and the methylation intensity at PTEN CpG islands, and further disclosed that LMP1-mediated NF-κB up-regulated DNMT3b transcription by binding to DNMT3b promoter, leading to the higher methylation intensity at PTEN CpG islands and ultimately silencing tumor suppressor PTEN in NPC. The gene discussed is PTEN; the disease is nasopharyngeal carcinoma.