AIM: To explore the therapeutic efficacy and influencing factors of differentiated thyroid cancer (DTC) after the first postoperative 131I treatment. METHODS: We retrospectively analyzed the clinical data of 116 DTC patients treated with 131I　for the first time after thyroid cancer surgery in the Department of Nuclear Medicine of the First Affiliated Hospital of Wannan Medical College, analysed their therapeutic efficacy, and Univariate and multivariate Logistic analyses were performed for the factors that may affect the efficacy of the treatment, respectively, and established ROC curves to analyse the diagnostic and ER efficacy of those with psTg and TTR that had a significant effect on the multifactorial Logistic analyses. RESULTS: In DTC patients who were followed up 3-9 months after the first postoperative 131I treatment, 69.0% (80/116) achieved ER. Univariate analysis revealed no statistical significance between ER and NER groups in terms of age, gender, TSH, TgVR, maximum tumour diameter, presence of lymph node metastasis, bilaterality of tumour, multifocality and clinical stage (P>0.05). While 131I dose, nsTg, psTg, TgV and TTR（Tg/TSH ratio） were statistically significant (P<0.05). The results of multifactorial Logistic analysis showed that psTg and TTR were independent risk factors for the first 131I treatment after DTC, with a psTg OR of 5.950 (95% CI 1.437-24.639, P<0.05) and a TTR OR of 4.137 (95%CI 1.073-15.947, P<0.05). The best threshold value of psTg for ROC curve analysis to predict the efficacy of the first postoperative 131I treatment for DTC was 8.935 μg/L, with a sensitivity of 80.6%, a specificity of 83.6%, and a Yuden's index of 0.64. And the best threshold value of TTR for predicting the efficacy of the first postoperative 131I treatment for DTC was 125.72 ng/mIU, with a sensitivity, specificity of 80.6% and 91.2%, and the Yuden index was 0.618. psTg and TTR areas under the curve were 0.839 and 0.833, respectively. psTg<8.935 μg/L patients achieved ER after 3-9 months of follow-up in DTC patients (67/74, 90.5%). psTg>8.935 μg/L patients achieved ER (13/42, 30.95%). Correspondingly TTR<125.72 ng/mIU achieved ER (65/72, 90.2%). psTg>125.72 ng/mIU achieved ER (15/44, 34.1%). CONCLUSION: The efficacy of the first 131I treatment after surgery for differentiated thyroid cancer is significant. psTg and TTR are independent risk factors for the first 131I treatment after DTC and have an important predictive value of efficacy.