Objective To investigate the application value of energy spectrum CT parameters in differential diagnosis of benign and malignant thyroid lesions. Methods Ninety-six patients who underwent neck energy spectrum CT for cervical lumps during the period from February 2017 to February 2018 were divided into the benign group and the malignant group according to the surgical and pathological results. The lesions, normal thyroid tissues, common carotid artery iodine content (IC) and water content (WC), arterial standard iodine content (NICA), normal thyroid standard iodine content (NICT) and energy spectrum slope of curve (γHU) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of relevant energy spectrum parameters for the nature of thyroid lesions. Results Compared with the benign group, IC lesions, NICT and γHU were significantly larger in the malignant group (P<0.05), but there was no significant difference in the other parameters between the two groups (P>0.05). With the results of pathological diagnosis as the golden standard, the ROC curves for the diagnosis of thyroid lesions by IC lesion, NICT and γHU were drawn. The results showed that the areas under the curves were 0.712, 0.698 and 0.702, respectively, and the cut-off values were 3.15 mg/ml, 0.52 and 3.70, respectively. The sensitivities, specificities and accuracy rates were 73.02%, 71.05% and 72.27%, 49.21%, 81.58% and 61.39%, and 66.67%, 76.32% and 70.30%, respectively. Conclusion The various parameters of energy spectrum CT play an important role in differential diagnosis of benign and malignant thyroid lesions.