Here, we demonstrate that TUFT1 promotes AKT phosphorylation but not AKT expression in RCC cells while inhibition of PI3K pathway also suppresses the phosphorylation of AKT and RCC cell growth, migration and EMT, indicating TUFT1 exerts oncogenic functions in RCC through PI3K/AKT signaling pathway. Here, TUFT1 is linked to renal cell carcinoma.