Lung cancer is the major cause of cancer-related deaths around the world. Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, contributed to the majority of mortalities and showed different clinical outcomes in prognosis. Tumor-infiltrated immune cells at the tumor site are associated with better survival and immunotherapy response. Thus, it is essential to further investigate the molecular mechanisms and new prognostic biomarkers of lung adenocarcinoma development and progression. In this study, a six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was established to predict the prognosis of LUAD patients, as well as predictive value. The prognostic risk model was also significantly associated with the infiltration of immune cells in LUAD microenvironments. To sum up, a novel immune-related six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was identified that could predict LUAD survival and is highly related to B cells and dendritic cells, which may provide a theoretical basis of personalized treatment for targeted immunotherapy.