The tumor suppressor gene nitrogen permease regulator-like 2(NPRL2) NPRL2 expressed obviously in many normal human tissues, but reduced in expression in many human tumors significantly. In this study, we detected the expression of NPRL2 in 78 clear cell renal cell carcinoma (ccRCC) by immunohistochemistry and correlated it with clinicopathological parameters. Meanwhile, the function of NPRL2 in human ccRCC was further explored after transfected recombinant expressing plasmids pEGFP-N1-NPRL2 into human renal cancer 786-0 cells. NPRL2 protein showed high expression in 67 of 78 cases of adjacent normal tissues (85.9 %), which was significantly higher than that in ccRCC tissues (23/78, 29.5 %). Clinic pathological analysis showed that NPRL2 expression was significantly correlated with histological grade (P = 0.044), TNM stage (P = 0.025) and lymph node metastasis (P = 0.028). MTT assay demonstrated that NPRL2 could obviously inhibit renal cancer cell proliferation. Flow cytometric analysis revealed that NPRL2 could induce renal cancer cells apoptosis and arrest the cell cycle in G0/G1 phase. In conclusion, NPRL2 is closely correlated to unfavourable pathological, proliferation and apoptotic features in ccRCC.