Non-small cell lung cancer (NSCLC) is a prevalent malignant tumor, and the commonly treatment modalities include surgery, radiotherapy, chemotherapy, etc. Currently, CT-guided percutaneous radiofrequency ablation (RFA) for the treatment of cancers has been widely performed. This study aimed to evaluate the safety and efficacy of this therapy in NSCLC patients. Thirty-five NSCLC patients were enrolled in this study and all received CT-guided percutaneous RFA therapy. The outcome measures included the changes in forced respiratory volume in the first second (FEV1), total lung volume (TLC), lesion size and computed tomography (CT) values of the region of interest (ROI) before and after treatment. The main efficacy measures comprised complete tumor ablation and local recurrence after initial treatment, as well as the objective response rate (ORR) and disease control rate (DCR) after 6 months of treatment. After receiving CT-guided percutaneous RFA therapy, the target lesion was effectively controlled and CT values gradually decreased. Besides, no significant changes were observed in the patient's lung function, postoperative complications were experienced by a total of 10 patients, primarily including pneumothorax, infection, lung hollowing. Fortunately, all these complications were successfully managed with appropriate treatment. Following the initial RFA treatment, 31 patients (88.57%) achieved complete ablation, while 6 patients experienced local recurrence. After 6 months of treatment, the ORR and DCR were found to be 68.57% and 82.86% respectively. CT-guided percutaneous RFA has demonstrated favorable safety and efficacy in the treatment of patients with NSCLC at different stages, which represented a promising therapeutic modality.