Objective To investigate the clinical value of radioiodine 131I ablation with SPECT/CT fusion imaging for evaluating lymph node metastasis in differentiated thyroid cancer (DTC). Methods The clinical data of 100 patients with DTC who were admitted to our hospital from January 2016 to December 2017 were retrospectively analyzed, all patients underwent the SPECT/CT fusion imaging and CT examination. Results The 131I-WBI showed that of the 300 patients, 110 patients had simple thyroid residuals, 95 had metastases, and 20 had been completely removed. There were 680 positive lesions including 330 residual lesions, and 350 metastatic lesions, of which 140 lymph nodes metastasis from the neck or mediastinum, and 210 cases of distant metastasis. The SPECT/ CT fusion imaging showed that the there were 120 patients with residual thyroid alone and 104 cases with metastatic disease. There were 712 positive lesions, 378 residual thyroid lesions, and 410 metastatic lesions, of which 160 were cervical or mediastinal lymph node metastases and 250 distant metastases. The surgical results showed that there were 110 cases of simple thyroid residue, 104 cases of metastasis, 398 residual lesions and 413 metastatic lesions, of which 152 were cervical or mediastinal lymph node metastasis and 261 were distant metastasis. The sensitivity, specificity and accuracy of SPECT/CT in diagnosing DTC metastases were significantly higher than those in 131I-WBI (P<0.05). The detection rate of lymph node and distant metastasis in SPECT/CT was significantly higher than that of 131I-WBI (P<0.05). Conclusion SPECT/CT can significantly improve the diagnostic rate of regional lymph node metastasis in differentiated thyroid cancer and is worth recommending.