Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer(NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry(IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor(KDR) and NRP-1 copy number gain(CNG) was assessed by fluorescence in situ hybridization(FISH). The distributions of overall survival(OS) and progression-free survival(PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG(+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue(χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs(χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status(P<0.05), but not age, gender or pathology type(P>0.05). VEGFR2 showed a strong correlation with NRP-1(Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG(Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression(P<0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis(P<0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC. Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) can be biomarkers for clinical treatment. the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer (NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry (IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor (KDR) and NRP-1 copy number gain (CNG) was assessed by fluorescence in situ hybridization (FISH). The distributions of overall survival (OS) and progression- PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test. Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG were detected in 32.5% and 30 % of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue (χ2 = 11.22, P = 0.001; χ2 = 9.82, P = 0.001, respectively) CNGs (χ2 = 4.39, P = 0.036; χ2 = 3.95, P = 0.046, respectively). Statistical significance of the correlation between histological grade, clinical TNM stage and the lymph node status (P <0.05) (Rs = 0.32, P = 0.04). Significant differences were observed with KDR and NRP-1 CNG (Rs = 0.32, P = 0.04) in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expressions (P <0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis (P <0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC.