RATIONALE AND OBJECTIVES: To evaluate the ability of dual-energy CT(DECT)-based quantitative parameters and radiomics features to differentiate solid lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC). METHODS: This study included 213 patients diagnosed with ADC and SCC who underwent DECT scans at two centers from November 2022 to December 2023. Patients at center 1 were randomly divided into training (n = 114) and internal test set (n = 50) in a 7:3 ratio, with center 2 serving as the external test set (n = 49). Radiologic and clinical data were combined to establish a clinical-radiologic model. Ten types of DECT energy images including conventional images, iodine density (ID), effective atomic number (Z RESULTS: The independent predictors of the clinical-radiological model included age, gender, and central or peripheral location, and the AUCs for the training set, internal test set, and external test set were 0.808, 0.837, and 0.802. The quantification model incorporated 40 keV CT values, Z CONCLUSION: The combined model, integrating quantitative parameters and radiomics features from DECT multi-energy images with clinical-radiological characteristics, can be used as a non-invasive tool to differentiate ADC from SCC.