Objective To investigate the application value of 64 slice spiral CT plain scan, enhanced scan and perfusion imaging in diagnosis and differential diagnosis of thyroid nodules. Methods 45 cases thyroid nodules(25 benign disease and 20 malignant disease),which were confirmed by surgery and pathology,were analyzed retrospectively. All patients underwent CT plain scan, perfusion scanning and enhanced scan, while the parameters of perfusion such as blood flow (BF), Patlak blood volume (P-BV), permeability (Per)and time-density curve generation (TDC), were measured and statistical analysis. Results The difference of the shape, boundary, internal cyst incidence, membrane integrity and enlarged lymph nodes between Benign and malignant nodules was statistically significant (P<0.05). While the difference of thenumber of nodules and calcification rate was not statistically significant(P>0.05). The inter-group comparison displayed that therewas statistically significant difference in Per value and TDC between benign and malignant nodules (P<0.05), then there was no significant difference between benign group and malignant group in BF and P-BV value (P>0.05). Conclusion The routine CT plain scan, enhanced scan, and perfusion imaging can reflect the characteristics of benign and malignant thyroid nodules, which has an important guiding significance for clinical treatment and the choice of surgical approach.