Objective To observe the expressions of phosphorylated eukaryotic translation initiation factor 4E (p-eIF4E) and phospho-eIF4E-binding protein 1 (p-4EBP1) and investigate their associations with clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). Methods We detected the expressions of p-eIF4E and p-4EBP1 proteins by immunohistochemistry in NPC tissues (n=314 cases), and analyzed the associations between the expressions of p-eIF4E and p-4EBP1 proteins and clinicopathological features and prognosis in NPC by SPSS16.0. Results Positive rates of p-eIF4E and p-4EBP-1 proteins in NPC were 74.2% (233/314) and 72.9% (229/314), respectively. There were significantly higher expressions of p-eIF4E and p-4EBP-1 proteins in the cases with lymph node metastasis than in those without lymph node metastasis. However, no significant correlations were observed between the expressions of p-eIF4E and p-4EBP-1 proteins and the age, gender, histological type, and clinical stage. There was significantly positive relationship between p-eIF4E and p-4EBP1 protein expressions in NPC. The overall survival rates were higher in the NPC patients with negative expressions of p-eIF4E and p-4EBP1 proteins than in those with positive expressions. The positive expressions of p-eIF4E and p-4EBP1 proteins were identified as the independent poor prognostic factors in NPC. Conclusion The over-expression of p-eIF4E and p-4EBP-1 proteins may be closely related to the occurrence, development and adverse prognosis of NPC. Hence, p-eIF4E and p-4EBP1 proteins are expected to be molecular markers for clinical diagnosis and prognosis of NPC.