There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA–urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features. We retrieved HCC characteristic lncRNAs,lncRNA-UCA1andlncRNA-WRAP53, based on the microarray signature profiling (released by LncRNADisease database). Quantitative reverse-transcriptase polymerase chain reaction assay (RT-qPCR) was then used to evaluate the expression of selected lncRNAs in the serum of 160 participants. Furthermore, in 20 of 82 HCC cases involved in the study, we examined the expression of lncRNA-UCA1andlncRNA-WRAP53in 20 HCC tissues and adjacent nontumor tissues and analyzed its correlation with the serum level of these lncRNAs. The prognostic significance of the investigated parameters in HCC patients was explored. We found thatlncRNA-UCA1andlncRNA-WRAP53were significantly higher in sera of HCC than those with chronic HCV infection or healthy volunteers. Our data suggested that the increased expression ofUCA1andWRAP53was associated with advanced clinical parameters in HCC. Of note, tissue levels of the chosen lncRNAs strongly correlate with their sera level. The combination of both lncRNAs with serum alpha fetoprotein resulted in improved sensitivity to 100%. The median follow-up period was 21.5 months.LncRNA-WRAP53was significant independent prognostic markers in relapse-free survival.LncRNA-UCA1andlncRNA-WRAP53upregulation may serve as novel serum biomarkers for HCC diagnosis and prognosis.