Objective: To explore the mechanism of circRNA (circ_0000218)/miR-139-3p/SRY-box transcription factor 2 (SOX2) axis in mediating the proliferation and metastasis of renal cell carcinoma cells. Methods: qRT-PCR was used to detect the expression of circ_0000218 and miR-139-3p in renal cell carcinoma tissues and cells, as well as the regulatory relationship between circ_0000218 and miR-139-3p in renal cancer cells. Subsequently, CCK-8 and Transwell experiments were used to detect the role of over expressed circ_0000218 or miR-139-3p mimics in cell proliferation, migration and invasion. The expression of miR-139-3p in RCC samples and its survival and prognosis information were predicted by StarBase database. Furthermore, Western blot was used to detect the effect of circ_0000218 or miR-139-3p on the expression of SOX2 in RCC cells. Finally, we use CircInteractome and TargetScan to predict, the double luciferase reporter gene experiment was verified the target relationship between circ_0000218 and miR-139-3p, miR-139-3p and SOX2. Results: Circ_0000218 was significantly up-regulated in renal cell carcinoma tissues and cell lines, and its high expression level was significantly correlated with T stage increased, local lymph node metastasis and distant metastasis. Overexpression of circ_0000218 promotes the proliferation and metastasis of RCC cells. The expression of miR-139-3p was low in renal cancer tissues and cells, and StarBase database predicted that its low expression was positively correlated with survival time of renal cancer patients. There is a negative correlation between circ_0000218 and miR-139-3p expression. The underlying mechanism suggests that circ_0000218 can promote the proliferation and metastasis of RCC by regulating miR-139-3p/SOX2 axis. Conclusion: In renal cell carcinoma, the circ_0000218 promotes the proliferation and metastasis of RCC cells by targeting on miR-139-3p/SOX2 axis, and may be used as a diagnostic bio-marker and therapeutic target.