All in all, this study demonstrated that circ_0054537, miR-640 and NPTX2 were aberrantly expressed in human RCC, and silencing circ_0054537 could suppress malignant progression of RCC in vitro and in vivo by sponging miR-640 to regulate NPTX2 expression. Here, NPTX2 is linked to renal cell carcinoma.