Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.