Background. Expression of long noncoding RNA (lncRNA) ELF3 antisense RNA 1 (ELF3-AS1) is observed in some cancers, while its role in hepatocellular carcinoma (HCC) is unclear. The study aimed to investigate the relationship between ELF3-AS1 and HCC based on database, bioinformatics, and statistical analysis. Methods. In this study, Kruskal–Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan–Meier method, Cox regression analysis, gene set enrichment analysis (GSEA), and immunoinfiltration analysis were used to assess the relationship between ELF3-AS1 expression and clinical characteristics of HCC patients, the relationship between ELF3-AS1 expression and prognosis of HCC patients, and the possible functions of ELF3-AS1 in HCC. Results. High expression of ELF3-AS1 in patients with HCC was related to T stage ( P  < 0.001), gender ( P  = 0.006), residual tumor ( P  = 0.008), histologic grade ( P  < 0.001), adjacent hepatic tissue inflammation ( P  = 0.011), AFP ( P  < 0.001), and vascular invasion ( P  = 0.028). High ELF3-AS1 expression was associated with poor overall survival (OS) ( P  = 0.001) and DSS ( P  = 0.047). ELF3-AS1 expression ( P  = 0.011) was independently correlated with OS in HCC patients. In the high ELF3-AS1 expression group, GPCR-radioligand binding, M phase, Class A/1 (rhodopsin-like receptors), cell cycle checkpoints, translation, mitotic metaphase and anaphase, signaling by robo receptors, keratinization, and rRNA processing were differentially enriched by GESA. ELF3-AS1 expression was associated with immune infiltrating cells. Conclusions. ELF3-AS1 expression was associated with poor prognosis in HCC. ELF3-AS1 expression was significantly associated with immune infiltration. ELF3-AS1 is a promising biomarker that can be used for the diagnosis and prognosis of HCC.