Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, is the highest diagnosed head and neck cancer in East Asia. However, the underlying mechanism of EBV to the tumor initiation, metastasis and recurrence of NPC is not fully characterized. EBV encoded transmembrane proteins LMP1 and LMP2A were found overexpressed in NPC tumors and the exogenous expression of LMP2A in NPC cells could induce EMT and increase the side populations. However the exact signaling pathway leading to NPC tumorigenesis has not been well characterized. Preliminary experiments showed that LMP2A significantly increased Bmi-1’s oncogenic expression, yet its mechanism remained to be identified. Bmi-1 is involved in the regulation of cancer stem cells, malignant tumors, and epithelial-to-mesenchymal transition (EMT) transformation and plays an important role in the occurrence of NPC. LMP2A are consistently expressed in the EBV-associated epithelial tumor NPC, and inhibit the autocrine secretion of IL-6 from NPC cell lines. However, the LMP1 expression was associated with increased phosphorylated Stat3 levels.