Taken together, our results suggested that eIF5A2 is a promising target to overcome hypoxia-induced chemoresistance in NSCLC, and cisplatin chemotherapy combined with eIF5A2 targeted therapy could effectively hinder NSCLC development, which will benefit patients with advanced or relapsed NSCLC who develop chemotherapy resistance. Here, EIF5A2 is linked to non-small cell lung carcinoma.