Nasopharyngeal carcinoma (NPC) is one of the common cancers among Chinese living in South China, Taiwan, Singapore and other countries. The etiological factors have not been clearly identified yet. So far, no any major gene related with hereditary factor has been identified in NPC carcinogenesis; however, some environmental factors, such as consumption of salted fish and Chinese herbs in Hong Kong and long term exposure to the sulfuric acid vapor in Taiwan have been suspected to be related to NPC induction, while Epstein-Barr virus (EBV) has been proposed to be closely associated with NPC pathogenesis. To investigate the relationship between NPC and EBV, we have established and characterized ten NPC cell lines. After extensive investigation, we conclude that EBV can establish an infection only in secretory component (SC) protein expressed- nasopharyngeal neoplastic cells but not nasopharyngeal metaplastic epithelial cells, which led us to use the IgA receptor mediated endocytosis of EBV-IgA-SC method to infect NPC cells. These observations imply that EBV may play more important role in the tumor progression stage rather than in the tumor initiation stage of the NPC carcinogenesis process. Furthermore, using the in vitro and in vivo systems to analyze the response of NPC host genes to EBV infection, we found that EBV can not turn on any host gene which is not expressed in NPC cells, but can enhance the gene expression in tumor cells which express this gene. These investigations consolidate and expand our hypothesis that EBV may play an important role in enhancement of NPC progression but not involve in the initiation and promotion stage of NPC pathogenesis. This is of fundamental importance to our concept of the EBV-associated NPC and may provide basic concepts for the selection of effective therapeutic strategy and avoidance of less effective EBV vaccination.