Objective: To explore the role of inflammatory markers NLR, MLR, PLR, and MPV in the early assessment of lymph node and distant metastasis in patients with non-small cell lung cancer (NSCLC). Methods: This retrospective study involved 411 newly diagnosed NSCLC patients admitted to the People’s Hospital of Lu’an City between 2018 and 2023. Fasting venous blood samples were collected from all patients upon admission for complete blood count analysis, with the calculation of NLR, MLR, and PLR, and the measurement of MPV. Patient information including age, gender, comorbidities, smoking history, alcohol consumption, pathological type, and clinical stage was collected via the electronic medical record system. The correlation between NLR, MLR, PLR, and MPV with lymph node and distant metastasis in NSCLC patients was assessed. Results: Compared with NSCLC patients without metastasis, those with lymph node or distant metastasis showed significantly higher levels of NLR, MLR, and PLR (P < 0.001) and a significantly lower MPV (P < 0.001). ROC curve analysis revealed that the AUCs for NLR, MLR, PLR, and MPV in differentiating NSCLC with metastasis were 0.777, 0.788, 0.697, and 0.620, respectively. Correlation analysis showed that NLR, MLR, and PLR were positively correlated with clinical stage (r = 0.504, P < 0.001; r = 0.498, P < 0.001; r = 0.369, P < 0.001), while MPV was weakly negatively correlated with clinical stage (r = -0.212, P < 0.001). Conclusion: The inflammatory markers NLR, MLR, PLR, and MPV have significant clinical value in the early assessment of lymph node and distant metastasis in NSCLC patients and may provide useful reference for clinicians in rapid prediction.