Abstract: Objective To investigate the effects of morphine on the invasion and migration of human lung adenocarcinoma A549 cells line. Methods Human lung adenocarcinoma A549 cells were cultured in vitro for 24 hours and were randomly divided into 4 groups： control group， 0.3 μg／ml morphine group， 3 μg／ml morphine group and 30 μg／ml morphine group. The cells in the control group were treated with normal saline， whereas cells in the morphine groups were treated with morphine at different concentrations（0.3， 3， and 30 μg／ml）. The invasion of cells was determined by transwell assay. The migration of cells was determined using the wound healing assay. The levels of matrix metalloproteinase-2（MMP-2）， MMP-9， ezrin and fascin proteins were assessed by Western blotting analysis. Results Compared with the control group， morphine treatment increased tumor cell invasion and migration abilities at concentrations above 3 μg／ml（P＜0.05）. The expressions of MMP-2， MMP-9， ezrin and fascin proteins were significantly increased compared with the control group after treatment of morphine at the concentration of 30 μg／ml for 48 hours（P＜0.05）. Conclusion Morphine increase tumor cell invasion and migration of human lung adenocarcinoma A549 cells line in a dose-dependent manner， which may be associated with the upregulation expressions of MMP-2， MMP-9， ezrin and fascin proteins.