Abstract: Radiation kills tumor cells mainly via DNA double-strand breaks ( DSBs ). However, tumor cells have different levels of DSB-repairing capacity. The level of DSB repair is related to the cell radiosensitivity. In human cells, there are two DSB repair pathways. The first is non-homologous end joining ( NHEJ ), which is based on DNA-dependent protein kinases ( DNA-PKs ). The second is homologous recombination repair ( HR ), which is based on ataxia telangiectasia mutated ( ATM ). In humans, NHEJ is the main repair pathway. DNA-PK catalytic subunits ( DNA-PKcs ) are the primary functional units of DNA-PKs. The activities of DNA-PKcs are necessary for NHEJ and DSB repair. Studies on the structures and functions of ATM and DNA-PKcs, on their expression levels in tumor cells, as well as on tumor radiosensitivity are increasing. The expression levels of ATM and DNA-PKcs are found to be related to the cell radiosensitivity. This article reviews the studies on the functions and expression of these two proteins in tumor cells, and their relationships with cell radiosensitivity.