Objective To explore the influencing factors of postoperative 131 I treatment response in intermediate- and low-risk differentiated thyroid carcinoma (DTC) and evaluate the predictive value of thyroglobulin (Tg) levels. Methods Clinical data from 389 intermediate- and low-risk DTC patients who underwent surgery followed by 131 I therapy were retrospectively analyzed. The follow-up duration ranged from 6 to 204 months (median 75 months). Patients were categorized into an excellent response (ER) group (n=310) and a non-excellent response (NER) group (n=79) based on treatment outcomes. Baseline characteristics were compared between groups, and multivariate analysis was performed to identify independent predictors. Results Significant differences in gender, T stage, N stage, cumulative 131 I dose, preoperative thyroid function (TSH, FT3, FT4, Tg), and surgical approach were observed between ER and NER groups (P＜0.05). Multivariate analysis revealed that N stage, cumulative 131 I dose, and Tg levels were independent predictors of treatment outcomes (P＜0.05). ROC curve analysis demonstrated strong predictive performance of stimulated thyroglobulin(sTg) and inhibitory thyroglobulin(iTg) for ER/NER, with AUC values of 0.773-0.886 (P＜0.05). Conclusion N stage, cumulative 131 I dose, and Tg (sTgand iTg)levels are independent predictors of postoperative 131 I treatment response in intermediate- and low-risk DTC. Tg serves as a critical dynamic follow-up marker for predicting 131 I therapeutic efficacy