In this study, we showed that overexpression of Annexin A2 enhanced cisplatin resistance of A549, H460 and H1650 cells, whereas inhibition of Annexin A2 could selectively increase cisplatin sensitivity of A549/DDP cells both in vitro and in vivo, which suggested an important role of Annexin A2 in cisplatin resistance in NSCLC cells. Here, ANXA2 is linked to non-small cell lung carcinoma.