Abstract: Objective: To investigate the expression of Stat3, the signal transducer and activator of transcription factor 3, and its downstream targets, including BCL-XL, Cyclin D1 and VEGF, in nasopharyngeal carcinoma (NPC) and to explore the mechanism of tumorigenesis of NPC. Methods: The expression of Stat3, BCL-XL, Cyclin D1 and VEGF proteins in paraffin-embedded specimens of 29 cases with chronic nasopharyngitis, 60 cases of NPC and 28 cases of lymph node metastasis was studied using immunohistochemical staining (ABC). Results: The positive rate of Stat3, BCL-XL, Cyclin D1 and VEGF in chronic nasopharyngitis was 41.38% (12/29), 34.48% (10/29), 27.59% (8/29) and 24.13% (7/29), respectively; the expression of Stat3, BCL-XL, Cyclin D1 and VEGF in nasopharyngeal carcinoma was 73.33% (44/60), 68.33% (41/60), 55.00 % (33/60) and 80.00% (48/60), respectively, with significant differences when NPC was compared to chronic nasopharyngitis; the positive rate of Stat3, BCL-XL, Cyclin D1 and VEGF in lymph node metastasis was 85.71% (24/28), 75.00% (21/28), 71.43% (20/28) and 82.14% (23/28), respectively, with significant differences when lymph node metastasis was compared to chronic nasopharyngitis. There was no significant difference in the expression of these 4 proteins between NPC and lymph node metastasis. Spearman correlation analysis showed there was a significant correlation between the expression of Stat3, Cyclin D1 and VEGF in the NPC and lymph node metastasis. Conclusions: Stat3 and VEGF may play an important role in the development of NPC, and the VEGF gene may be directly regulated by Stat3 protein.