For the first time, we reported possible tumor-related driver genes, alterations in specific chromosomal regions of CNV, and critical genes associated with targeted therapy in TFEB/6p21/VEGFA-amplified renal cell carcinoma (Table 1), which deepened our understanding of the diagnosis and molecular genetic alterations of TFEB/6p21/VEGFA-amplified renal cell carcinoma and provided new information for their prognosis and treatment. Here, TFEB is linked to hereditary clear cell renal cell carcinoma.