Objective:To evaluate the performance of combined quantitative analysis of thyroid blood flow and static imaging data in the differential diagnosis of thyroid nodules. Method: Thyroid blood flow and static imaging were performed in 165 patients with thyroid nodules. Patients were divided into a benign thyroid nodule group (BTN, n=135) and a malignant thyroid nodule group (MTN, n=30) based on the results of post-surgical pathologic examination. Carotid artery thyroid transit times (CTTT), perfusion ratio of thyroid nodule blood/thyroid blood (TNB/TB), and perfusion ratio of thyroid nodule blood/carotid artery blood (TNB/CAB) were measured using thyroid blood flow imaging. The ratios between thyroid nodule and ipsilateral submandibular gland (TN/SG) and thyroid nodule and normal thyroid tissue (TN/T) were measured from thyroid static imaging. The differences between the BTN and MTN groups were compared. Results: 1) CTTT was markedly lower in the MTN group than the BTN group, the difference being statistically significant. 2) TNB/TB and TNB/CAB were both significantly higher in MTN than BTN groups. 3) TN/T was significantly lower in MTN group than BTN group. 4) TN/SG was lower in MTN group than BTN group, but the difference was not statistically significant. 5) Using the combination of CTTT and TN/T, the sensitivity, specificity and accuracy were 93.1%, 95.3% and 94.9% respectively for the diagnosis of MTN. Using the combination of CTTT, TNB/TB and TN/T, the sensitivity, specificity and accuracy changed to 89.7%, 100%, and 98.1% respectively. 6) Correlation analysis demonstrated a significant correlation between TN/T and TNB/TB (r=-0.384, P=0.036) and TNB/CAB (r=-0.466, P=0.009) in the MTN group. Conclusion: The combination of quantitative markers from thyroid blood flow and thyroid static imaging had high specificity and accuracy in differential diagnosis of benign and malignant thyroid nodules, thus providing an important imaging diagnostic approach.