Background: Lack of expression of Epithelial Membrane Protein-2(EMP2) in Nasopharyngeal carcinoma (NPC) is associated with adverse prognosticators and might confer tumor aggressiveness through hampering its interaction with specific membrane protein; and as Human Herpes Viruses linked to etiology of NPC, the aim of this study was to find out the relationship between EME2and these viruses. Methodology: In this study patients with NPC were investigated retrospectively. EMP2 expression was demonstrated by immunohistochemistry using n EMP2 antibody. EBV, CMV and HSV were identified by polymerase chain Reaction (PCR). Results: loss of EMP2 (negative) was identified in 10/92 (10.9%), P < 0.04; 10/53 (18.9%), P <0.05 and 4/18(22.2%), P<0.001 of EBV, CMV and HSV, respectively. Conclusion: In NPC, there is significant correlation between loss of expression of EMP2 and human herpes virtues (EBV, CMV and HSV).