Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study reports an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). We retrospectively evaluated patients who underwent combined ablation and resection in an HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. The clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. A total of 22 patients were enrolled in this study. Twenty patients underwent unilateral procedures, while the other two patients underwent bilateral procedures. Ablations were performed before lung resection in 21 patients; only 1 patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14,076 μGym2. The median hospital postoperative length of stay was 2 days. The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in an HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.