Objective MicroRNAs are involved in the occurrence and development of many cancers, and microRNA-218-5p (miR-218-5p) has been proven to play an important role in cancer development. However, the specific mechanism of miR-218-5p’s effect on the development of lung adenocarcinoma (LUAD) has not been clarified. Methods The expression of miR-218-5p in LUAD tissues was analyzed in TCGA data, and the mRNA expression of miR-218-5p and EGLN3 in human lung normal and human LUAD cell lines was detected by qRT-PCR. Western blot was used to detect the protein expression levels of key AKT/ mTOR signaling pathway proteins and EGLN3 in tumor cells. The microRNA-target relationship between miR-218-5p and EGLN3 was predicted by bioinformatics method and confirmed by luciferase reporter gene detection. The roles of miR-218-5p and EGLN3 in LUAD were measured by CCK-8, colony formation, scratch healing, and Transwell assays. Results miR-218-5p was underexpressed in LUAD. Overexpression of miR-218-5p inhibited the proliferation, migration and invasion of LUAD cells and the activation of the AKT/ mTOR signaling pathway. EGLN3 was the downstream target gene of miR-218-5p, which was highly expressed in LUAD. Overexpression of EGLN3 weakened the inhibitory effect of miR-218-5p on proliferation, migration and invasion by LUAD cells. Conclusions miR-218-5p inhibited proliferation, migration, and invasion in LUAD cells by negatively affecting EGLN3 expression.