The entire body of a patient with cancer is exposed to low-dose levels of radiation (mGy) during radiation therapy. The safety and biological impact of such exposure to low-dose radiation on the human body are largely unknown. The fingernail is a highly proliferative tissue, and its growth can be monitored during radiation treatment to analyze early effects of low-dose radiation. The fingernails of 30 patients who received external beam radiotherapy (EBRT) were used in this study to investigate the change in nail growth during fractionated radiotherapy. Lead shields were applied to some fingers to create dose variance within individual patients. The absorbed dose was measured, and the relationship between the dose and change in nail growth rate was analyzed. Other factors, including serum albumin, hemoglobin level, body weight index, age, gender and chemotherapy, were also subjected to multivariate analysis. Fingernails from patients received an average of 0.96 mGy per treatment fraction. We observed a surprising decline in fingernail growth rate during radiotherapy, which was more prominent in the nonshielded fingernails with a relatively high-absorbed dose. Such growth delay could be observed as early as one week postirradiation and lasted the entire treatment course. Using fingernail growth as a novel marker for radioresponse, the current study showed that exposure to very low-dose ionizing radiation has previously unrecognized early effects on human tissue.