Liver cancer is a leading cause of cancer‑associated mortality worldwide. Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. The aim of the present study was to identify long non‑coding RNA (lncRNAs) as diagnostic biomarkers for HCC. The lncRNA and mRNA expression profiles of a large group of patients with HCC were obtained from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) and the differentially expressed mRNAs (DEmRNAs) were identified by bioinformatics analysis. Using feature selection procedure and a classification model, the optimal diagnostic lncRNA biomarkers for HCC were identified. Classification models, including random forests, decision tree and support vector machine (SVM), were established to distinguish between HCC and normal tissues. DEmRNAs co‑expressed with the lncRNAs were considered as targets of DElncRNAs. Functional annotation of DEmRNAs co‑expressed with these lncRNAs biomarkers was performed. Receiver operating characteristic curve analysis of lncRNAs biomarkers was conducted. A total of 3,177 lncRNAs and 15,183 mRNAs between HCC and normal tissues were obtained. RP11‑486O12.2, RP11‑863K10.7, LINC01093 and RP11‑273G15.2 were identified as optimal diagnostic lncRNA biomarkers for HCC that were co‑expressed with 273, 69, 76 and 1 DEmRNAs, respectively. The area under the curve values of the random forest model, decision tree model and SVM model were 0.992, 0.927 and 0.992, and the specificity and sensitivity of the three models were 100.0 and 95.6, 92.0 and 98.3 and 98.0 and 97.2%, respectively. 'PPAR signaling pathway' and 'retinol metabolism' were two significantly enriched target pathways of DElncRNAs. The present study identified four DElncRNAs, including RP11‑486O12.2, RP11‑863K10.7, LINC01093 and RP11‑273G15.2, as potential diagnostic biomarkers of HCC. Functional annotation of target DEmRNAs provided novel evidence for examining the precise roles of lncRNA in HCC.