S100A9 was originally regarded as a regulator of immune response and a mediator of the inflammatory process. Recent studies have suggested that S100A9 expression plays an important role during tumor development, progression and metastasis in various cancers. The present study aimed to investigate the expression and prognostic role of S100A9 in clear cell renal cell carcinoma (ccRCC).S100A9 expression was examined by immunohistochemical staining in 152 patients who underwent surgical resection due to ccRCC. The correlation between S100A9 expression and clinicopathological data and its prognostic role were evaluated in patients with ccRCC.S100A9 revealed high expression in 37 cores (12.6%) of ccRCC. S100A9 expression was significantly associated with T stage (P < .001) and Fuhrman nuclear grade (P < .001), but not with patient age (P = .821) and sex (P = .317). Survival analysis revealed that high S100A9 expression is an independent factor for unfavorable disease-free survival (hazard ratio, 2.423; 95% confidence interval, 1.044-5.621; P = .039) and disease-specific survival (hazard ratio, 2.428; 95% confidence interval, 1.130-5.214; P = .023) in patients with ccRCC.S100A9 expression can be a useful prognostic factor in patients with ccRCC.