In this study, we demonstrated that endogenous ADAM9 expression was significantly up-regulated in aggressive lung adenocarcinoma cells, and ADAM9 could activate the expression of CDH2. Down-regulation of miR-218, which resulted from low transcription of pri-mir-218-1, led to CDH2 over-expression in aggressive lung cancer cells. Here, ADAM9 is linked to lung adenocarcinoma.