Background: Contrast-enhanced chest computed tomography (CT) is useful for the detection and follow-up of patients with lung cancer. However, reaching balance between diagnostic image quality, radiation dose, and iodixanol dose is a cause of concern. Objectives: To investigate the clinical value of adaptive statistical iterative reconstruction (ASIR) in reducing the iodixanol content and radiation dose during contrast-enhanced chest CT scan for patients diagnosed with lung masses/nodules based on the analysis of image quality. Methods: This prospective study was conducted on 80 patients diagnosed with nodules or masses, who required contrast-enhanced chest CT scans. The experimental group (n = 40) was subjected to iohexol at a high concentration (350 mgI/L) with a tube voltage of 120 kVp and a filter back projection (FBP) reconstruction algorithm. The comparison group (n = 40) was subject to iodixanol at a lower concentration (270 mgI/L) with a tube voltage of 100 kVp and ASIR (blending ratio, 40%). The radiation dose and total iodixanol content, as well as subjective and objective evaluations of image quality, were analyzed and compared. Results: The two groups obtained non-significantly different subjective scores for five structures detected in the lung window and five structures detected in the mediastinal window, as well as the overall image (P > 0.05 for all). Both the two-group images obtained diagnosis-acceptable scores (≥ 3 points) on displays of 10 structures and overall image quality. The mean CT value of vessels (100 kVp vs. 120 kVp: 314.90 ± 23.42 vs. 308.93 ± 21.40; P > 0.05), standard deviation (13.03 ± 0.88 vs.12.83 ± 0.90; P > 0.05), and contrast-to-noise ratio (20.77 ± 2.20 vs. 20.36 ± 1.94; P > 0.05) were not significantly different between two groups. However, the CT dose index, dose-length product, effective dose, and total iodine dose were reduced by 27.58%, 36.65%, 36.59%, and 22.86% in the 100-kVp group compared to the 120-kVp group. Conclusions: The ASIR showed great potential in reducing the radiation dose and iodine contrast dose, while maintaining good image quality and providing strong confidence for the diagnosis of lung cancer.