This study investigates NONO-TFE3-regulated proteins in TFE3 rRCC. Stable NONO-TFE3 knockdown and control UOK109 cells were used to generate whole-cell lysates (WCL) and extracellular vesicles (EVs), which were analyzed by LC-MS/MS. The dataset provides quantitative proteomic profiles to identify differentially expressed proteins involved in TFE3 rRCC progression.