Clear cell renal cell carcinoma (CCRCC) is the most common pathological type of renal cell carcinoma and the main cause of renal carcinoma mortality. NDRG2, a new member of the N-Myc downstream-regulated gene (NDRG) family, is a focus for study at present. Up to now, its expression and function in carcinoma remain unclear. The aim of this study was to investigate its expression in CCRCC tissues and several renal carcinoma cell lines. The expression of NDRG2 was evaluated in renal cell carcinoma cell lines, tumor and adjacent non-tumor tissues from same clear cell renal cell carcinoma patients, by using immunohistochemistry, immunofluorescence, RT-PCR and Western blot. By immunohistochemistry and immunofluorescence we found that NDRG2 was predominantly located in the cytoplasm and membrane of renal carcinoma cancer cells, and the positive rate of NDRG2 in renal carcinoma specimens was 30.3% (40/132), which is significantly lower than 91.67% (121/132) in normal renal tissues (p<0.01). The average staining score in normal renal tissues was significantly higher than renal carcinoma (6.12+/-1.84 versus 2.65+/-1.23, p<0.01). Moreover, NDRG2 mRNA and protein were down-regulated in 6 fresh CCRCC tissues compared with their adjacent noncancerous tissues and normal tissues. Its expression was also lower in the human CCRCC-derived cell lines A-498 and 786-O than in the human proximal tubular cell lines HK-2 and HKC. These results indicated that NDRG2 might play an important role in the carcinogenesis and development of CCRCC and may function as a tumor suppressor in CCRCC.