To evaluate safety and therapeutic efficacy of sodium glycididazole (CMNa) combined with ¹³¹I radiotherapy for differentiated thyroid carcinoma (DTC), the 60 patients of DTC therapeutic protocols were selected and divided into 3 groups of the DTC 4.44 GBq ¹³¹I, DTC 3.70 GBq ¹³¹I, and combination of DTC 3.70 GBq ¹³¹I with CMNa, and the 20 patients of Graves' Disease were selected as the control group. Peripheral blood was sampled at ¹³¹I pre-treatment of 1 day, and ¹³¹I post-treatment of 7, 91, and 182 days, thus analyzing lymphocyte micronucleus scores and karyotyping profiles. Compared with the control group, the lymphocyte micronucleus and chromosome mutation rates in ¹³¹I treated DTC increased after post-treatment of 7 days, recovered after post-treatment of 91 days, and did not bounce after post-treatment of 182 days. The micronucleus and chromosome mutation rates in the combination of DTC 3.70 GBq ¹³¹I with CMNa showed less significant variation than other treated DTC groups. Our results demonstrate that micronucleus assay and karyotyping analysis are favorable to evaluate ¹³¹I radiotherapy for DTC. The combination of the CMNa with ¹³¹I radiotherapy was safe for DTC patients without affecting the long-term therapeutic outcomes.