The highly malignant nature of lung adenocarcinoma (LUAD) makes its early diagnosis and prognostic assessment particularly important. However, whether the CXC subfamily of chemokine receptors (CXCR) is involved in the development and prognosis of LUAD remains unclear. Here, differentially expressed genes (DEGs) associated with overall survival (OS) were selected from the cancer genome atlas (TCGA) dataset using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognostic gene signature was constructed, which was evaluated using Kaplan-Meier curves, receiver operating characteristics curves, nomogram curves, and an external gene expression omnibus (GEO) dataset. Finally, we verified the functions of the genes comprising the signature using the gene expression profiling interactive analysis (GEPIA) and the immune system interaction database (TISIDB) web portals. We constructed a 7-gene signature (SHC1, PRKCD, VEGFC, RPS6KA1, CAT, CDC25C, and GPI) that stratified patients into high- and low-risk categories. Notably, the risk score of the signature was a separate and effective predictor for OS (P < .001). Patients in the low-risk category had a better prognosis than those in the high-risk category. The receiver operating characteristics and nomogram curves verified the predictive power of the signature. Moreover, in both categories, biological processes and pathways associated with cell migration were enriched. Immune infiltration statuses differed between the 2 risk categories. Critically, the results from the GEPIA and TISIDB web portals indicated that the expression of the 7-gene signature was associated with survival, clinical stage, and immune subtypes of LUAD patients. We identified a CXCR-related gene signature that could assess prognosis and provide a reference for the diagnosis and treatment of LUAD.