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Patients with early-stage non-small cell lung cancer (NSCLC), even stage IA, are at substantial risk of relapse and death. We explored the distinct features of molecular alterations and immune-related gene expression in Formalin-fixed paraffin-embedded (FFPE) samples from 25 relapsed patients compared with 25 non-relapsed patients through using whole-exome sequencing and an immune oncology panel RNA sequencing platform. Results showed that the chemokine, cytolytic activity and tumour-associated antigen gene signatures exhibited significantly higher expression in non-relapsed tumours from stage IA lung adenocarcinoma (LUAD) than that in relapsed tumours. Besides, Kaplan–Meier survival analysis revealed that the gene signatures of chemokines and tumour-associated antigens were significantly associated with the patients’ disease-free survival (DFS), indicating their prognostic value in early-stage LUAD. Cytolytic activity displayed a similar trend but failed to reach statistical significance. These findings revealed a weakened immune phenotype in relapsed tumours and provide valuable information for improving the treatment management of these high-risk patients. Due to the overall small patient number in this study, these differences should be further validated in a larger cohort.