Radiotherapy is a common treatment for cancer, though its effectiveness can be limited due to radiation resistance and damage to healthy tissues. Increasing the sensitivity of cancer cells to radiation while protecting normal cells is crucial for improving treatment outcomes. This study aimed to evaluate the radiosensitizing effects of tolmetin on human colon cancer cells (HT-29) during radiotherapy. HT-29 cells were divided into groups, with one receiving X-ray radiation and another receiving both X-rays and tolmetin at different concentrations. Micronucleus formation and the nuclear division index were used to assess genotoxicity and cytotoxicity, respectively. The results showed a significant increase in micronuclei in the radiation-only group compared to the control group. Groups treated with tolmetin at concentrations of 75 and 100 μM also showed an increase in micronuclei, with the highest increase observed at concentrations of 100 and 150 μM. However, tolmetin did not alter the nuclear division index at any of the concentrations tested. The findings indicate that tolmetin effectively sensitizes HT-29 colon cancer cells to radiation in a concentration-dependent manner, without inducing cytotoxicity.