BackgroundHepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments.MethodsLncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts.ResultsLINC01116 and the PCGOLFML2Bare differentially and highly expressed in tumor tissues (bothP≤ 0.050). We found that LINC01116,TMSB15A,PLAU,OLFML2B,andMRC2have diagnostic potentials (all AUC ≥ 0.700, allP≤ 0.050) while LINC01116 andTMSB15Ahave prognostic significance (both adjustedP≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed thatMRC2,OLFML2B,PLAU, andTMSB15Aare negatively associated with the purity but positively associated with the specific cell types (allP< 0.050). Analysis of promoter methylation demonstrated thatMRC2,OLFML2B, andPLAUhave differential and high methylation levels in primary tumors (allP< 0.050). Validation results of the differential expressions and diagnostic potential ofOLFML2B(Oncomine) were consistent with those obtained in the TCGA cohort (P< 0.050, AUC > 0.700).ConclusionsDifferentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressedOLFML2Bcould be a diagnostic signature involved in HCC via immune infiltrates.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-023-02827-y.