We observed that the downregulation of PIK3R1 resulted in EMT, increased migration, colony formation, cell sphere, and tumor formation in renal cancer cells, suggesting that the reduction of PIK3R1 expression confers renal cancer cells a selective advantage to translocate, colonize and develop as mRCC, and that PIK3R1 may be involved in the progression and metastasis of RCC through the PI3K/AKT/GSK3β/CTNNB1 pathway. This evidence concerns the gene PIK3R1 and renal cell carcinoma.