Previously we reported that phosphorylated eIF4E is elevated in human head and neck squamous cell cancer. In the present study, our results showed there was a high positive expression of p-Mnk1 and p-eIF4E in NPC, but p-Mnk1 and p-eIF4E were significantly low and weak positive expression in the non-cancerous nasopharyngeal epithelia tissues. In this study, we further found that expression of p-Mnk1 and p-eIF4E was significantly positive correlation in NPC. It suggests that the AKT/mTOR and MAPK/MNKs signal pathway augment to promote the development and progression of NPC. Invasion and metastasis are the basic biological character which is TH-302 related to recurrence and also effect on NPC patients’ survival. The invasion and metastasis had correlation with vascular endothelial growth factor, cell adhesion and cellular degradation, and positive correlation with the protein of invasion and metastasis. The induction of VEGF protein by Akt is associated with increased phosphorylation and thus activation of p70S6K and eIF4E-binding protein 1. Our results indicated that expression of p-Mnk1 and p-eIF4E protein in the NPC patients with cervical lymph node metastasis was significant higher than those without lymph node metastasis. There was significantly negatively association between positive expression of p-Mnk1 and p-eIF4E and survival status of NPC patients. Interestingly, in this study, there was significant higher expression of p-eIF4E in metastatic NPC than that in the matched primary cancer. These results suggest that high expression of p-eIF4E and p-Mnk1 maybe play a critical role in promoting invasion and metastasis and relate with the poor progression of NPC patients. However, in our study, expression of p-Mnk1 in primary NPC was no significant difference compared with their matched metastatic/relapsed NPC. These results suggested that p-Mnk1 maybe the equal functions in different clinical stages of NPC. These data were from limited samples. We think the reason is further studies need to be done to investigate it with much samples. There are many factors that are related with NPC prognosis. Enhanced eIF4E phosphorylation has been observed in various solid tumors and lymphomas, and p-eIF4E overexpression is correlated with poor prognosis or recurrence, metastases in human tumors. Our results showed that the NPC patients with positive expression of p-Mnk1 and p-eIF4E had an obvious shorter survival time than these patients with negative staining of p-Mnk1 and p-eIF4E. The higher incidence of cervical lymph node metastasis without typical early clinical features and higher rate of loco-regional relapse compared with other head and neck cancers are the main factors on prognosis of NPC. Among a number of classical prognostic indicators for NPC, cervical lymph node metastases is the main one, besides other biological parameters. Fortunately, the early stage NPC patients are usually radio-and chemo-therapy sensitive.