Mnk1 specifically phosphorylate eIF4E at Ser209 which is the only phosphorylation site in eIF4E. Mnk and eIF4E interact with eIF4G bringing them into physical proximity to facilitate eIF4E phosphorylation. The eIF4E phosphorylation is the molecular basis of carcinogenesis. Overexpression and/or increased phosphorylation of eIF4E, now considered to be a Temozolomide proto-oncogene, leads to overexpression of certain proto-oncogenes, growth factors, and other cell cycle–related protein transcripts, which promotes proliferation and survival rate of tumor cell and effectively regulates cellular transformation and metastasis. Some studies have shown that p-eIF4E and p-Mnk1 were respectively correlated with human carcinogenesis and development, and the inhibition of the Mnk1/eIF4E pathway acted as a potential therapeutic target. Previous studies have confirmed that there is an overexpression of eIF4E in head and neck tumor including of NPC, and eIF4E can enhance NPC cell proliferation and cell cycle progression. However, whether the alterations of the expression of peIF4E and p-Mnk1 protein are associated with development and progression and clinicopathologic/prognostic implication for NPC has not been reported. In the current study, we have investigated the expression pattern of p-eIF4E and p-Mnk1 protein in 272 NPC cases and 85 non-cancerous nasopharyngeal epithelial specimens by Immunohistochemistry and determined the correlation between the expression of p-eIF4E and p-Mnk1 and clinicopathologic/prognostic characteristics in NPC. We found that higher expression of p-Mnk1 and p-eIF4E is associated with the cervical lymph node metastasis in NPC. The significantly positive correlation between p-Mnk1 and p-eIF4E expression indicates that eIF4E activation through the Mnk1 plays an important role in the progression of NPC. Moreover, high expression of p-eIF4E in addition to p-Mnk1 might predict poor prognosis of NPC. Increasing evidences have shown that Mnks and eIF4E play important roles in the pathogenesis and prognosis of many tumors. Mnks is an upstream kinase of eIF4E which its phosphorylation depends on kinase Mnks activity. The phosphorylation of eIF4E promotes proliferation and survival rate of tumor cell and are critical for malignant transformation and cancer progression. Mnk1 overexpression is sufficient to confer resistance to trastuzumab in cells that are previously sensitive to the treatment. The phosphorylated Mnk1 is required for the ability of Mnk1 to mediate resistance to trastuzumab. Mnk1 inhibitor leads to reduced cyclin D1 expression and causes inhibition of cell proliferation and cell death in human brain malignant lymphoma cell line. The significantly abnormal over-expression of p-eIF4E protein is found in a number of tumors including non-small cell lung cancer, breast cancer, gastric cancer, colon cancer, prostate cancer, penile squamous cell carcinoma,.