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Objective To investigate the expression of HLA-G and determine the prognostic value of HLA-G for lung adenocarcinoma. Methods The genomic alternation of HLA-G was analyzed using cBioPortal analytic tool. The expression of HLA-G was investigated immunohistochemically in 223 patients with lung adenocarcinoma. The correlation between HLA-G expression and clinicopathological features was analysed. The relationship between HLA-G expression and the survival rate of patients with lung adenocarcinoma was analyzed by Kaplan-Meier Plotter data. Results HLA-G was mainly amplified in lung adenocarcinoma. Patients with low expression of HLA-G had longer overall survival than those with high HLA-G expression. Conclusion HLA-G was found highly expressed in lung adenocarcinoma, and may serve as a prognostic factor and potential therapeutic target for lung adenocarcinoma.