In our study, knockdown and overexpression of NEDD4L respectively promoted and suppressed the invasive ability of ccRCC cells, and NEDD4L-KD significantly rescued the invasion and metastasis suppression imposed by KSRP-KD in Caki-1 cells and the Caki-1 xenograft model. Here, NEDD4L is linked to nonpapillary renal cell carcinoma.