Purpose: To investigate the expressions of S100 calcium-binding proteins A8 (S100A8) and S100 A9 (S100A9) in nasopharyngeal carcinoma (NPC) tissues and their correlation with clinical pathological characteristics and prognosis of NPC.Methods: Ninety-two NPC tissue samples and 92 nasopharyngitis tissue samples (controls) were collected. All the NPC patients were on follow-up for more than 5 years. The expressions of S100A8 and S100A9 were determined in these tissues by immunohistochemistry. The relationship between the expressions of S100A8 and S100A9, and the clinico-pathological features were analyzed by Spearman correlation analysis, and the results evaluated by Kaplan-Meier method.Results: The differences between their expressions in the two tissues were statistically significant (p < 0.05). Neither gender nor age was associated with expressions of S100A8 and S100A9 (p > 0.05), but they were closely related to the degree of differentiation, clinical stages and metastasis of lymph node (p < 0.05). The expression of S100A8 had significant positive correlation with the expression of S100A9 (r = 0.393, p = 0.000). Prognosis of patients with positive expressions of S100A8 and S100A9 was poor, when compared to patients with negative expressions of these proteins (p < 0.05).Conclusion: Expressions of S100A8 and S100A9 are closely related to the development of NPC. High expressions of the two proteins may have an important influence in the progress of tumor invasion but are associated with poor prognosis of NPC. These findings could be significant indicators of early diagnosis, effectiveness of treatment and prognosis of NPC.Keywords: S100A8, S100A9, Calcium-binding proteins, Prognosis, Nasopharyngeal carcinoma, Prognosi