The thyroid hormone controls, via its nuclear receptor TR1, intestinal crypt cell proliferation in the mouse. In order to understand whether this receptor also plays a role in intestinal regeneration after DNA damage, we applied a protocol of gamma-ray irradiation and monitored cell proliferation and apoptosis at several time points. In wild type mice, the dose of 8 Gray induced cell cycle arrest and apoptosis in intestinal crypts a few hours after irradiation. This phenomenon reverted 48h after irradiation. TR^0/0 mutant mice displayed a constant low level of proliferating cells and a high apoptosis rate during the period of study. At the molecular level, in TR^0/0 animals we observed a delay in the p53 phosphorylation induced by DNA damage. Looking for the expression of the protein-kinases responsible for p53 phosphorylation upon irradiation, we have focused on DNA-PKcs. The number of cells expressing DNA-PKcs in crypts remained high 48h after irradiation, specifically in TR mutants. Altogether, in TR^0/0 animals the rate of apoptosis in crypt cells remained high, apparently due to an elevated number of cells still presenting DNA damage. In conclusion, the TR gene plays a role in crypt cell homeostasis by regulating the rate of cell renewal and apoptosis induced by DNA damage.