Objective To investigate the expression of MAD2L1 in lung adenocarcinoma and its effect on the prognosis and immune microenvironment of patients. Methods The difference of MAD2L1 expression in lung adenocarcinoma tissue and normal lung tissue was analyzed by TCGA and GEO database. Survival analysis was carried out to evaluate the prognostic significance of MAD2L1 gene expression in lung adenocarcinoma patients. StarBase database was used to construct miRNA-MAD2L1 regulatory network of lung adenocarcinoma. The relation between the expression of MAD2L1 and immune cell infiltration in lung adenocarcinoma was analyzed by TIMER database. Results The expression of MAD2L1 was up-regulated in lung adenocarcinoma, and the high expression of MAD2L1 was significantly correlated with pathological stage and lymph node metastasis of lung adenocarcinoma. The patients with high expression of MAD2L1 had a poor prognosis. miR-101-3p/MAD2L1 axis was identified as the most potential upstream regulation pathway of MAD2L1 in lung adenocarcinoma. The expression level of MAD2L1 was significantly correlated with tumor immune cell infiltration and immune checkpoint expression. Conclusions MAD2L1 is highly expressed in lung adenocarcinoma, which is related to poor prognosis and tumor immune infiltration. MAD2L1 can be used as a potential target for the treatment of lung adenocarcinoma.