Abstract Objectives To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. Methods A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. Results SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P