Lung adenocarcinoma (LUAD) severely threatens the health of people owing to its lethality. Nonetheless, the underlying mechanisms on LUAD development remain unclear to a great extent. This work aimed to probe the functions of miR-218-5p in LUAD. MiR-218-5p and endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) were screened as differently downregulated and upregulated RNAs in LUAD, respectively, by bioinformatics analyses. The results of cell functional assays stated that enforced expression of miR-218-5p notably restrained cell viability, invasion, and migration in LUAD. MiR-218-5p may interact with 3’-untranslated region of ERO1A mRNA as analyzed by bioinformatics. Afterward, western blot and dual-luciferase reporter gene analyses were introduced to identify their interaction. ERO1A overexpression reversed the suppressive impacts of miR-218-5p on LUAD cell progression, indicating the implication of miR-218-5p/ERO1A axis in suppressing cancer development. We also observed that this regulatory axis suppressed angiogenesis in LUAD. Taken together, miR-218-5p/ERO1A axis exerted an imperative role in LUAD cell progression, which provides a valuable clue for the development of LUAD therapeutic regimen.