BACKGROUND: The localization of pulmonary nodules is crucial for surgical intervention. However, a safe, simple, and efficient method remains elusive. This study aims to evaluate the safety and feasibility of a newly developed preoperative localization method for pulmonary nodules called Rapid Localization of Pulmonary Nodules On-Site (RLPN-OS). METHODS: This study is a single-center, single-arm prospective investigation that collects and analyses the clinical data of patients who underwent RLPN-OS and lung resection, primarily evaluating the safety and feasibility of this technique. RESULTS: A total of 200 lung nodules from 190 patients who underwent RLPN-OS and partial lobectomy were included in this study. The success rate of localization was 98.0%, and minor intercostal bleeding was observed in 3 (1.5%) cases. All targeted lesions were located and resected successfully. No patients reported experiencing anxiety or pain during or after the procedure. CONCLUSIONS: This novel RLPN-OS technology represents a safe, feasible, patient-friendly, and cost-effective method for lung nodule localization. It has the potential to serve as an alternative to traditional CT-guided percutaneous localization techniques.