Objective:To investigate the risk factors and prognostic indicators of radioactive iodide refractory (RAIR) in differentiated thyroid cancer (DTC) with distant metastasis (DM).Methods:From January 2007 to November 2023, 140 DM-DTC patients who received 131I therapy in JiangYuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine were retrospectively conducted. According to the effect of 131I treatment, 84 cases in the RAIR group and 56 cases in the radioactive iodide efficient (RAIE) group were finally included. The general clinical data, B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E and telomerase reverse transcriptase promoter (TERTp) mutations were compared between the two groups by independent-sample t test, Mann-Whitney U test and χ2 test. Multiple logistic regression was used to analyze the influencing factors of RAIR. Results:There were significant differences between the RAIR group and the RAIE group in age, age≥55 years, tumor maximum diameter, cumulative dose of radioactive iodide, type of metastasis and preoperative thyroglobulin (pre-Tg) ( χ2 values: 7.78 and 9.03, t values: 2.44-2.74, z=-3.92, all P<0.05). The TERTp mutation rate in RAIR group was 39.39%(26/66), which was significantly higher than that in RAIE group (2.17%(1/46); χ2=20.97, P<0.001). The BRAF V600E mutation rate was 41.79%(28/67) in the RAIR group and 40.00%(20/50) in the RAIE group, with no significant difference ( χ2=0.04, P=0.846). Logistic regression analysis found that high pre-Tg level and TERTp mutation were independent risk factors for RAIR occurrence. Conclusion:TERTp mutation and high pre-Tg level are independent risk factors for RAIR occurrence, and they may be potential indicators for predicting RAIR.