OBJECTIVE: Lung cancer is one of the most prevalent malignancies worldwide, with 80–85% of cases diagnosed as non-small cell lung cancer (NSCLC). The majority of NSCLC patients present with advanced disease, contributing to high mortality and limited treatment options. Angiogenesis, a crucial process in cancer progression, is largely regulated by growth factors and cy-tokines. Vascular Endothelial Growth Factor (VEGF) is a key regulator of angiogenesis. Asymmetric Dimethyl Arginine (ADMA) inhibits endothelial nitric oxide synthase (eNOS), leading to reduced nitric oxide (NO) release and subsequent endothelial dysfunction. The aim of this study is to investigate the serum levels of ADMA, NO, VEGF and several tumor markers including Carcinoembryonic Antigen (CEA), Cancer Antigen 125 (CA 125), Neuron Specific Enolase (NSE), Lactate dehydrogenase (LDH) and Cyfra 21-1 in NSCLC patients to assess their potential role in early diagnosis, tumor invasion, and staging of the disease. METHODS: Our study consisted of 56 newly diagnosed NSCLC patients and 32 controls with similar demographic charac-teristics. Patients with chronic diseases and inflammatory disorders were excluded. Statistical analysis was conducted using R Statistical Software. RESULTS: In our study, compared to the control group, the serum VEGF, NO, ADMA, CA 125, CEA, Cyfra 21-1 and NSE levels were significantly higher in NSCLC group (p=0.001, p=0.013, p=0.041, p<0.001, p<0.001, p<0.001 and p=0.001, respectively). In the diagnosis of NSCLC, Cyfra 21-1 exhibited the highest diagnostic efficacy with a 71% sensitivity and 94% specificity. The combination of VEGF, CA125, and Cyfra 21-1 showed a 73% sensitivity and 100% specificity, while the combination of CA125, CEA, and Cyfra 21-1 achieved an 85% sensitivity and 91% specificity. CONCLUSION: Our study revealed that the serum concentrations of VEGF, NO, ADMA, CA125, Cyfra 21-1, CEA, and NSE were significantly elevated in patients with NSCLC compared to the control group, and that levels of Cyfra 21-1, LDH, and NSE increased with advancing TNM stage. The combination of markers distinguished NSCLC with high sensitivity and specificity. Further studies involving larger populations, including those with benign lung diseases, are needed to validate and expand upon our findings.