Abstract: Radiotherapy is important for cancer treatment. However, some patients still experience relapse and exhibit radiation resistance. Mammalian target of rapamycin (mTOR) is the main effector molecule in PI3K/AKT signaling. This molecule is found in two structurally and functionally distinct multi-protein complexes known as the mTOR complex 1 and mTOR complex 2. The mTOR signaling pathway controls the growth, proliferation, survival, and apoptosis of cancer cells. This pathway is closely related to tumorigenesis and treatment response, and is used in sensitizing radiotherapy. mTOR inhibitors regulate radio-sensitization through multiple mechanisms, including cell cycle alterations, DNA repair modulation, and tumor hypoxia reduction. Preclinical studies showed that mTOR inhibitors with tolerable toxicity may be used as an effective modality to overcome radio-resistant tumors. Responses to mTOR inhibitors vary depending on the cell lines. Molecular markers can be used to select suitable patients. Further studies are needed to completely understand the use of mTOR inhibitors in radio-sensitization.