Background: Extracellular matrix metalloproteinase inducer (EMMPRIN), as a glycoprotein member enriching on surfaces of many malignant tumor cells, may play a certain role in promoting the tumor progression; furthermore, it also has something to do with tumor invasion, metastasis and angiogenesis. The study has been carried out to investigate the role of EMMPRIN in renal clear cell carcinoma, as well as its clinical significance. Methods: We have adopted a variety of methods, including Real-time quantitative PCR, Western blot and immunohistochemistry, to discover the expression of EMMPRIN in primary ccRCC clinical specimens and cell lines; as a result, EMMPRIN was knocked down in 786-O cells by siRNA (small interfering RNA). In addition, we have also adopted CCK-8 and Colony Formation to examine the biological functions and inhibitory effects of the knockdown investigated in 786-O. Results: The study found that the expression of EMMPRIN was higher in renal cancer than in normal tissues, which led to the down-regulation of MMP-2 and MMP-9, and the up-regulation of E-cadherin. The same result was found in the expression of EMMPRIN in renal cancer cell lines, being higher than that in normal renal epithelial cells. EMMPRIN knockdown by RNA interference led to cell proliferation, migration and invasion, conversely resulting in increased expression of E-cadherin in renal clear cell carcinoma, while the level of Vimentin remained unchanged. Conclusions: It is found in this study that EMMPRIN is over-expressed in kidney cancer, and EMMPRIN expression is related to tumor tissues and cell lines of renal cancer. It is therefore concluded that high EMMPRIN expression can be taken as a predictor of poor prognosis in patients suffering from kidney tumor, and EMMPRIN may be taken as a latent therapeutic gene of kidney cancer.