Objective To explore the clinical application of single photon emission computed tomography (SPECT) / X-ray computed tomography (CT) imaging in patients of differentiated thyroid carcinoma (DTC) with 131I treatment after DTC removal. Methods 119 patients undergoing thyroid DTC patients with total or partial resection (Male 22 cases, female 97 cases) to remove residual thyroid tissue by 131I (referred to as the removal treatment) 5 ~ 7d, 131I-SPECT with 2.5mA X-ray tube device and 131I whole body scan (131I-WBS scan), all the results were confirmed by pathology, other imaging (B-mode ultrasonography , CT) and clinical follow-up one year to determine DTC 397 metastasis lesions. Results The total 377 of DTC metastasis or recurrence lesions were found in patients by 131I-SPECT with 2.5mA X-ray tube device fusion imaging, accounting for 95%. The false negative lesions were 9, accounted for 2%, and 11 false positive extra nodal lesions, accounting for 3%. 131I-WBS imaging found 324 DTC metastasis or recurrence lesions, accounting for 82%. The false negative lesions were 64, accounted for 16% and 9 false positive extra nodal lesions, accounting for 2%. There were significantly difference in founding lesions number between two methods (P <0.01). Conclusion 131 I-SPECT with 2.5mA X- ray tube device imaging in patients of differentiated thyroid carcinoma (DTC) with 131I treatment after DTC removal can accurately locate the recurrence and metastasis lesions of DTC and improve the detection rate of lesions. It would be helpful for re-staging of DTC and provide the basis for further treatment of patients.