Background. Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown.Methods. We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan-Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration.Results. The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD.Conclusion. In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.