Objective To explore the clinical significance of inhibitor of NF-κB (IκB) family in lung adenocarcinoma (LUAD) through bioinformatics analysis. Methods The differentially expressed genes of IκB family in LUAD were screened by R language for survival analysis. The correlation between the expression of IκB family genes and clinicopathological characteristics was analyzed by R language, and the genes related to survival rate were selected for further study. GO and KEGG enrichment analyses were performed with LinkedOmics. The infiltration of immune cells was analyzed with TIMER. The correlation between the candidate genes and the prognosis of LUAD was analyzed through COX model. Results The expression levels of NF-κB inhibitor δ (NFKBID) and NF-κB inhibitor Zeta (NFKBIZ) were significantly downregulated in tumor tissues, and the patients with low expression levels of NFKBID and NFKBIZ had shorter overall survival. NFKBID and NFKBIZ were significantly correlated with T stage of LUAD. Enrichment analysis showed that low expression levels of NFKBID and NFKBIZ were correlated with energy metabolism and protein expression and transport. The expression levels of NFKBID and NFKBIZ were positively correlated with the infiltration of B cells, CD4+ T cells, neutrophils, and dendritic cells. COX analysis indicated that NFKBIZ could be an independent prognostic factor for LUAD. Conclusion The expression levels of NFKBID and NFKBIZ were significantly downregulated in tumor tissues, and were correlated with overall survival. NFKBID and NFKBIZ could be involved in the occurrence and development of LUAD by regulating glycometabolism and multiple immune cells infiltration. NFKBIZ could be considered as an independent prognostic factor for LUAD.