〔Abstract〕 Objective To investigate the role of murine double minute 2(MDM2) in dihydroartemisinin′s(DHA) inhibition of lung adenocarcinoma cell proliferation and migration. Methods CCK8 assay was used to detect the inhibitory effect of gradient concentrations of DHA(0, 5, 10, 25, 50 and 100 μmol/L) and time gradients(0, 24, 48, and 72 h) on the proliferation of lung adenocarcinoma A549 and PC9 cells, and the half maximal inhibitory concentrate(IC50) were calculated respectively. Colony formation and scratch assays were used to detect the inhibitory effects of DHA on colony formation and migration of A549 and PC9 cells. Western blot was used to detect the inhibitory effects of DHA on MDM2 expression and epithelial-mesenchymal transition(EMT)-related proteins E-cadherin and N-cadherin. The promoting effects of MDM2 on proliferation, migration and EMT of lung adenocarcinoma cells were verified by small interfering RNA-mediated knockdown of MDM2(si-MDM2). The reversal effects of MDM2 overexpression on DHA′s inhibition on the proliferation and migration of A549 and PC9 cells were observed. Results DHA inhibited the proliferation of A549 and PC9 cells in a dose-and time-dependent manner, with IC50 values of 30.57 and 78.61 μmol/L, respectively. Compared with the Control group, A549 and PC9 cells had significantly decreased colony formation(both P