Objective To investigate the 64 slice spiral CT imaging features of benign and malignant thyroid nodules and its value in in the differential diagnosis. Methods The clinical and 64 slice spiral CT imaging data of 50 patients with thyroid nodular lesions were analyzed retrospectively. The imaging findings (diameter, number, shape, boundary, calcification, etc.) were observed and compared between different properties (benign and malignant) of thyroid nodules. Meanwhile, based on the pathological results, the sensitivity, specificity and accuracy of 64 slice spiral CT in the diagnosis of thyroid nodules were analyzed. Results 20 cases of malignant nodules and 30 cases of benign nodules were confirmed pathologically. Malignant thyroid nodules which were solitary, irregular, with fuzzy boundaries, with sand like calcification and adjacent structure involvement accounted for 80.00%, 70.00%, 75.00%, 55.00% and 55.00% respectively which were significantly higher than those of the benign nodules (33.33%, 26.67%, 26.67%, 20.00%, 0.00%) (P<0.05). There were no significant differences in diameter, cystic degeneration and density of benign thyroid nodules (P>0.05). The sensitivity, specificity and accuracy of MSCT in the diagnosis of thyroid malignant nodules were 85.00%, 90.00% and 88.00%, respectively. Conclusion 64 slice spiral CT examination can display the number, shape, boundary and adjacent structure invasion or not, which is beneficial to distinguish benign and malignant thyroid nodules.