The incidence of kidney cancer has been increasing globally during the past two decades. Renal cell carcinoma (RCC) is the most aggressive subtype of kidney cancer, which usually deteriorates with epithelial-mesenchymal transition (EMT) that facilitates the migration and invasion of cancer cells. Till now, the underlying mechanism remains unclear. In this study, we demonstrated that programmed death ligand 1 (PD-L1/B7-H1/CD274) could induce EMT and enhance RCC cell cancer stemness through up-regulation of SREBP-1c. Furthermore, we found that PD-L1 is up-regulated in human RCC metastases. These results, taken together, provide evidence for a novel mechanism of PD-L1 in RCC progression, suggesting that there is a close relationship between EMT and immune escape signaling pathways in RCC.