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Purpose The assessment of Programmed death-ligand 1 (PD-L1) expression has become a game changer in the treatment of patients with advanced non-small cell lung cancer (NSCLC). We aimed to investigate the ability of Radiomics applied to computed tomography (CT) in predicting PD-L1 expression in patients with advanced NSCLC. Methods By applying texture analysis, we retrospectively analyzed 72 patients with advanced NSCLC. The datasets were randomly split into a training cohort (2/3) and a validation cohort (1/3). Forty radiomic features were extracted by manually drawing tumor volumes of interest (VOIs) on baseline contrast-enhanced CT. After selecting features on the training cohort, two predictive models were created using binary logistic regression, one for PD-L1 values ≥ 50% and the other for values between 1 and 49%. The two models were analyzed with ROC curves and tested in the validation cohort. Results The Radiomic Score (Rad-Score) for PD-L1 values ≥ 50%, which consisted of Skewness and Low Gray-Level Zone Emphasis (GLZLM_LGZE), presented a cut-off value of − 0.745 with an area under the curve (AUC) of 0.811 and 0.789 in the training and validation cohort, respectively. The Rad-Score for PD-L1 values between 1 and 49% consisted of Sphericity, Skewness, Conv_Q3 and Gray Level Non-Uniformity (GLZLM_GLNU), showing a cut-off value of 0.111 with AUC of 0.763 and 0.806 in the two population, respectively. Conclusion Rad-Scores obtained from CT texture analysis could be useful for predicting PD-L1 expression and guiding the therapeutic choice in patients with advanced NSCLC.