In the context of pulmonary nodules detected in imaging, there is currently a lack of highly effective and non-invasive methods for both diagnosing and prognosticating lung squamous cell carcinoma (LUSC). Therefore, in this study, we explored the potential of plasma-derived extracellular vesicles (EVs) with a new nanomaterial as a source of candidate biomarkers to distinguish between benign and malignant pulmonary nodules and predict the prognosis of LUSC patients.