Antiapoptosis and invasion are the causes for the failure of conventional radiotherapy and chemotherapy in human renal carcinomas. Osteopontin (OPN), a ligand for vß3 integrin and CD44 receptors, is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, OPN has been detected in human renal carcinomas and assessed as a potential prognostic marker of renal carcinomas. However, the function and mechanism of OPN in renal carcinomas remain unknown. In this study, we used OPN siRNA to silence the expression of OPN in renal carcinoma Caki-1 cells. Silent effect showed that sequence-specific siRNA targeting OPN suppressed OPN mRNA expression by 81% and OPN protein level by 91% in vitro. The apoptosis ability was significantly increased while the invasion ability was decreased in Caki-1 cells transfected with OPN siRNA. Western blot demonstrated that the effects of OPN silence were significantly accompanied by the activation of mitochondria-related apoptosis pathway involving cytochrome c, Apaf-1, cleaved caspase-3 and Bcl-2/Bax, and the downregulation of invasion-related proteins of MMP-2 and uPA expression. These results suggest that the downregulation of OPN expression can induce apoptosis increase and invasion suppression in renal carcinoma Caki-1 cells through mitochondria-related apoptosis pathway and MMP-2 and uPA-related invasion proteins, respectively.