Abstract: Objective To explore the expression and clinical significance of neuropilin-1 (NRP-1) in epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma. Methods Fifty cases with positive EGFR mutation and 28 cases with negative EGFR mutation were screened. The expression of NRP-1 and VEGFR2 was detected by immunohistochemistry. The correlation between clinical parameters and NRP-1 and VEGFR2 was analyzed. Results The positive expression rates of NRP-1 and VEGFR2 in EGFR mutant positive lung adenocarcinoma were significantly higher than those in EGFR mutant negative lung adenocarcinoma (P<0.05). The expression of NRP-1 and VEGFR2 in EGFR-positive lung adenocarcinoma was correlated with the size of tumors, TNM stage, differentiation degree of tumors and lymph node metastasis (P<0.05), but not with age and sex (P>0.05). Kaplan-Meier survival curve showed that progression-free survival (PFS) in low-expression group of NRP-1 and VEGFR2 was significantly longer than that in high-expression group (P < 0.05). The expression of NRP-1 and VEGFR2 was positively correlated. COX multivariate analysis showed that both NRP-1 and VEGFR2 were independent risk factors for poor prognosis of EGFR-positive lung adenocarcinoma patients (P<0.05). Conclusions NRP-1 is highly expressed in EGFR-positive lung adenocarcinoma tissues. NRP-1 plays an important role in the occurrence, development and metastasis of lung adenocarcinoma. NRP-1 may be a new target for targeted therapy of EGFR-positive lung adenocarcinoma.