413 Background: Interleukin-32 (IL-32) is a proinflammatory cytokine, which acts as an important pathogenetic factor in various diseases and malignancies. However, the clinical significance of IL-32 expression in renal cell carcinoma has not been previously investigated. Methods: We examined 112 patients with localized clear cell renal cell carcinoma (CCRCC) who underwent nephrectomy. The clinicopathologic data were obtained by retrospective review and the expression levels of IL-32 were studied by immunohistochemistry. Tumors were classified into four scores based on the staining intensity (0, no staining intensity; 1, weak; 2, intermediate; 3, strong). The cases with staining intensities from 0 to 2 were included in the IL-32 low expression group (LEG); whereas, those with staining intensity of 3 were considered the IL-32 high expression group (HEG). Correlations between IL-32 expression and clinicopathologic features were determined. Results: Staining intensities were determined for all cases as follows: 26 cases (23.2%) (score 0), 43 cases (38.4%) (score 1), 31 cases (27.7%) (score 2), and 12 cases (10.7%) (score 3). IL-32 HEG showed a higher recurrence rate compared to the IL-32 LEG (50% vs. 13%, P=0.001). For survival rates, the 5-year recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) rates were lower in the IL-32 HEG compared with the IL-32 LEG (RFS, 87% vs. 50%, P = 0.001; DSS, 92% vs. 58.3%, P < 0.001; OS, 84% vs. 58.3%, P = 0.026, respectively). Univariate analyses showed that Fuhrman nuclear grade and high IL-32 expression were significant prognostic factors for predicting RFS, DSS, and OS in CCRCC; while, multivariate analyses indicated Fuhrman nuclear grade and high IL-32 expression (RFS, HR, 4.932, P = 0.009; DSS, HR 6.736, P = 0.002; OS, HR, 2.992, P = 0.037, respectively) were still independent risk factors. Conclusions: IL-32 overexpression was associated with high recurrence rates and low RFS, DSS, and OS, suggesting that it could be a novel prognostic factor for predicting outcomes in patients with CCRCC after a nephrectomy.