Loss of phosphatase and tensin homologue (PTEN), the major negative regulator of the PI3K/AKT pathway, triggers cellular senescence through a p53-dependent pathway called PTEN-loss-induced cellular senescence (PICS). Although the mTOR pathway has been consistently shown to have a critical function in cellular Senescence, the exact roles of mTORC1 and mTORC2 in PICS are not well known. In this study, we show that mTOR is a critical relay molecule downstream of PI3K/AKT and upstream of p53 in PICS. mTOR kinase, a major component of mTORC1 and mTORC2, directly binds p53 and phosphorylates it at serine 15. We found that mTORC1 and mTORC2 compete with MDM2 and increase the stability of p53, finally induces cellular senescence via accumulation of the cell cycle inhibitor, p21. In embryonic fibroblasts of PTEN-knockout mice, PTEN deficiency also induces mTORC1 and mTORC2 to bind to p53 instead of MDM2, leading to cellular senescence. These results collectively demonstrate that p53 phosphorylation at S15 by mTOR kinase activity is indispensable for PICS and active AKT-induced cellular senescence.