To explore the value of applying computed tomography (CT) radiomics based on different CT-enhanced phases to determine the immunotherapeutic efficacy of non-small cell lung cancer (NSCLC).106 patients with NSCLC who underwent immunotherapy are randomly divided into training (74) and validation (32) groups. CT-enhanced arterial and venous phase images of patients before treatment are collected. Region-of-interest (ROI) is segmented on the CT-enhanced images, and the radiomic features are extracted. One-way analysis of variance and least absolute shrinkage and selection operator (LASSO) are used to screen the optimal radiomics features and analyze the association between radiomics features and immunotherapy efficacy. The area under receiver-operated characteristic curves (AUC) along with the sensitivity and specificity are computed to evaluate diagnostic effectiveness.LASSO regression analysis screens and selects 6 and 8 optimal features in the arterial and venous phases images, respectively. Applying to the training group, AUCs based on CT-enhanced arterial and venous phase images are 0.867 (95% CI:0.82-0.94) and 0.880 (95% CI:0.86-0.91) with the sensitivities of 73.91% and 76.19%, and specificities of 66.67% and 72.19%, respectively, while in validation group, AUCs of the arterial and venous phase images are 0.732 (95% CI:0.71-0.78) and 0.832 (95% CI:0.78-0.91) with sensitivities of 75.00% and 76.00%, and specificities of 73.07% and 75.00%, respectively. There are no significant differences between AUC values computed from arterial phases and venous phases images in both training and validation groups (P <  0.05).The optimally selected radiomics features computed from CT-enhanced different-phase images can provide new imaging marks to evaluate efficacy of the targeted therapy in NSCLC with a high diagnostic value.