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Background The important role of the NFκBpathway in tumor development has long been recognized. but the role of the NFκB inhibitor family in liver cancer has not been studied. Hepatocellular carcinoma（HCC）has become a serious public health burden with high incidence, poor prognosis, and early detection, especially in Asia where hepatitis is prevalent. Methods The transcript level of the NFκB inhibitor family was investigated in HCC and normal tissues using Metabolic Gene Rapid Visualizer, UALCAN, and Tumor Immune Estimation Resource database（TIMER）respectively. Survival curves of NFKBIE were obtained using the Kaplan-Meier database. Genes co-expressed with NFKBIE in hepatocellular carcinoma were studied by LinkedOmics and Hepatocellular Carcinoma Database（HCCDB） respectively. Protein-protein interaction (PPI) Networks, gene ontology, and KEGG enrichment pathway analyses provide a novel method for investigating the NFKBIE mechanism in HCC. Using the TIMER database, the connection between immune infiltration and NFKBIE was determined. RNA-Seq was used to evaluate NFKBIE's function in HCC and its impact on proliferation and migration. Western Blot was used to confirm the expression of NFKBIE in HCC cell lines.In addition, we demonstrated NFKBIE overexpression in HCC using tissue microarrays encompassing 80 pairs of HCC and normal liver tissues. Results: NFKBIE was the only NFκBinhibitor in its family with high expression and a better prognosis in HCC.NFKBIE was correlated with clinical characteristics such as tumor grade, TP53 mutation status, and tumor stage.GSCA database suggested that NFKBIE might inhibit the PI3K/AKT, RAS/MAPK, RTK, and TSC/mTOR pathways. In addition, NFKBIE was significantly associated with B cell immune infiltration, and our RNA-Seq data showed that NFKBIE knockout significantly affected antigen presentation and hepatocellular carcinoma pathways. Immunohistochemistry on microarrays of tissue samples revealed that NFKBIE was overexpressed in various stages of HCC. Inhibition of NFKBIE also decreased the growth and migration of hepatocellular carcinoma cells. Conclusion： Due to its prognostic value and overexpression in hepatocellular carcinoma, NFKBIE distinguished itself from other NFκB inhibitors. As such, it may provide a novel prognostic indicator and immunotherapeutic target in HCC.