DEAD box RNA helicase 17 (DDX17) has been shown to be an RNA binding protein involved in RNA metabolism and associated with cancer progression. However, the biological role of DDX17 in the pathogenesis of lung adenocarcinoma (LUAD) has not been well characterized. Here, we demonstrated that DDX17 promoted the proliferation, migration and invasion of H1299 and A549 lung adenocarcinoma cells. Analyses of public datasets showed that DDX17 is upregulated in LUAD specimens. Our tumor xenograft models confirmed the in vivo promoting role of DDX17 in the growth and metastasis of LUAD. Mechanistic analyses further revealed that DDX17 protein interacts with the mRNA of MYL9 and MAGEA6 and upregulates their levels. MYL9 could mediate the function of DDX17 to regulate the actin cytoskeleton rearrangement and cell adhesion, particularly by modulating the stress fiber and focal adhesion formation, whereas DDX17 might inhibit the autophagy process through MAGEA6/AMPKα1 axis in LUAD cells. Collectively, our study revealed the oncogenic role and pathways of DDX17 in LUAD.