Abstract: Objective:To investigate the expression of AKT2, S100 A4 and MMP- 9 in nasopharyngeal carcinoma (NPC) and its clinical significance. Methods:Immunohistochemical technology (EliVision two steps) was applied to detect the ex -pression of AKT2, S100 A4 and MMP- 9 proteins in 50NPC tissue samples and25tissue samples of chronic nasopharyngi -tis. The relationship of AKT2, S100 A4 and MMP- 9 expression with clinical features of NPC and the correlations among the three proteins were analyzed. Results: The positive rates of AKT 2 (48.0% ,24/50), S 100 A4 (52.0% ,26/50) and MMP- 9 (74.0%,37/50) in NPC tissues were respectively higher than those in chronic nasopharyngitis tissues ( 8.0%,2/25), (0%,0/25), and (36.0%,9/25), P <0.01. The positive rates of AKT 2 and S 100 A4 were correlated with cervical lymph node metasta -ses and clinical stage (P<0.05) The positive rate of MMP- 9 was correlated with cervical lymph node metastases (P<0.05). The positive expression of the three proteins was not correlated with gender, age or T classification (P>0.05). The expres -sion of AKT2 and S 100 A4 was positively correlated with MMP-9 expression in NPC tissues (P<0.01). But the expression of AKT 2 was not correlated with S100 A4 expression (P>0.05). Conclusion:The increased expression of AKT2, S 100 A4 and MMP-9 may play a significant role in the occurrence, development and metastasis of NPC. AKT2 and S 100 A4 may pro-mote the development and metastasis of NPC by up-regulating the expression of MMP-9. Detection of AKT2, S100 A4 and MMP-9 is of great value for predicting the biological behaviors and metastasis of NPC.