Objectives: We aimed to investigate the relation between serum fibroblast growth factor (FGF) 23 levels and clinicopathologic features of stage 3B and 4 non-small cell lung cancer (NSCLC) patients without druggable alterations in genes as epidermal growth factor receptor (EGFR) or rearrangements of the anaplastic lymphoma kinase (ALK) or c-ROS oncogene 1 (ROS1), by comparing healthy control group. Methods: This was a prospective, single-center study. Newly diagnosed stage 3B and 4 NSCLC patients without druggable alterations in genes as EGFR, ALK or ROS1 and healthy control in similar age, without any chronic disease and vitamin D deficiency were enrolled in the study. Fibroblast growth factor 23 levels were compared between groups. Results: Forty men newly diagnosed stage 3B and 4 patients and 24 healthy men were enrolled. The median age of patients and controls were 54.7 and 53.1 years. The number of patients were 22 (55.0%) and 18 (45.0%) in stage 3B and stage 4 groups respectively. The mean FGF 23 level was calculated as 87.7±58.0 pg/ml in patients group and 63.1±11.4 pg/ml in control group (p=0.045). Fibroblast growth factor 23 levels were 85.5±42.5 pg/ml and 89.6±69.1 in metastatic and non-metastatic patients respectively (p=0.532). The median FGF 23 levels were 91.1±58.4 pg/ml and 92.5±60.8 pg/ ml in squamous cell carcinoma and adenocarcinoma groups respectively (p=0.926). Conclusion: Our study suggests that high FGF-FGFR interaction may be causative for stage 3B and 4 NSCLC without druggable alterations in genes as EGFR, ALK or ROS1 and is important in terms of suggesting the FGF pathway as a new treatment target in NSCLC patients.