OBJECTIVE: Considering the essential role of KRAS mutation in NSCLC and the limited experience of PET radiomic features in KRAS mutation, a prediction model was built in our current analysis. Our model aims to evaluate the status of KRAS mutants in lung adenocarcinoma by combining PET radiomics and machine learning. METHOD: Patients were retrospectively selected from our database and screened from the NSCLC radiogenomic dataset from TCIA. The dataset was randomly divided into three subgroups. Two open-source software programs, 3D Slicer and Python, were used to segment lung tumours and extract radiomic features from F-FDG-PET images. Feature selection was performed by the Mann-Whitney U test, Spearman's rank correlation coefficient, and RFE. Logistic regression was used to build the prediction models. AUCs from ROCs were used to compare the predictive abilities of the models. Calibration plots were obtained to examine the agreements of observed and predictive values in the validation and testing groups. DCA curves were performed to check the clinical impact of the best model. Finally, a nomogram was obtained to present the selected model. RESULTS: One hundred and nineteen patients with lung adenocarcinoma were included in our study. The whole group was divided into three datasets: a training set ( = 96), a validation set ( = 11), and a testing set ( = 12). In total, 1781 radiomic features were extracted from PET images. One hundred sixty-three predictive models were established according to each original feature group and their combinations. After model comparison and selection, one model, including wHLH_fo_IR, wHLH_glrlm_SRHGLE, wHLH_glszm_SAHGLE, and smoking habits, was validated with the highest predictive value. The model obtained AUCs of 0.731 (95% CI: 0.6190.843), 0.750 (95% CI: 0.2481.000), and 0.750 (95% CI: 0.448~1.000) in the training set, the validation set and the testing set, respectively. Results from calibration plots in validation and testing groups indicated that there was no departure between observed and predictive values in the two datasets ( = 0.377 and 0.861, respectively). CONCLUSIONS: Our model combining F-FDG-PET radiomics and machine learning indicated a good predictive ability of KRAS status in lung adenocarcinoma. It may be a helpful non-invasive method to screen the KRAS mutation status of heterogenous lung adenocarcinoma before selected biopsy sampling.