The aim of our study was to analyse the expression of CXCL16, ADAM10 and CXCR6 in renal cell carcinoma (RCC) tissue and to correlate the expression pattern with clinicopathologic data, including patient survival. Furthermore, we investigated CXCL16, ADAM10 and CXCR6 expressions by FACS, immunofluorescence and ELISA analysis in renal carcinoma cell lines. Our immunohistochemical analysis on tissue microarray of renal cancer samples of 104 patients revealed that ADAM10 correlated significantly with tumour stage, pathological nodal status, M status and lymphangiosis carcinomatosa. CXCL16, CXCR6 and ADAM10 were significantly increased in papillary carcinomas. Importantly, high levels of CXCL16 expression in renal cancer tissue correlated with better survival of patients, and CXCL16 correlated inversely to the tumour stage. In addition, inhibition of CXCL16 induced the migration of renal cancer cells assuming an anti-migratory function of transmembrane CXCL16. Taken together, our data demonstrate that downregulation of CXCL16 plays an important role in renal cancer development and progression, and that CXCL16 in RCC is an independent prognostic marker for better patient survival.