〔Abstract〕 Objective To analyze the value of multi-slice spiral computed tomography (MSCT) combined with energy spectrum computed tomography (CT) in evaluating the nature of pulmonary nodules lesions. Methods The clinical data of 121 patients with pulmonary nodules treated in Nanyang Second People's Hospital from January 2019 to January 2021 were retrospectively analyzed. All patients underwent MSCT and energy spectrum CT examination on admission, and pathological tissue biopsy examination was conducted at an selected time to record the nature of pulmonary nodules. MSCT parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and energy spectrum CT parameters [CT value of 70 keV and 80 keV single energy image, standardized iodine concentration (NIC)] were compared between malignant and benign pulmonary nodules, and the diagnostic value of MSCT combined with energy spectrum CT in pulmonary nodules was analyzed. Results Pathological biopsy results showed that there were 30 malignant and 91 benign pulmonary nodules in 121 patients. The MSCT parameters BF and energy spectrum CT parameters NIC of malignant pulmonary nodules were higher than those of the benign pulmonary nodules, and the differences were statistically significant (P < 0.05). The area under the curve (AUC) of benign and malignant pulmonary nodules detected by MSCT and energy spectrum CT alone and in combination were 0.836, 0.831 and 0.838, respectively. The best evaluation value could be obtained when BF and NIC were 97.570 mL·min-1 and 0.315, respectively. Conclusion MSCT combined with energy spectrum CT has a higher value in evaluating the nature of pulmonary nodules.