BACKGROUND Aberrant expression of long non-coding RNAs (lncRNAs) is associated with prognosis of gastric cancer, some of which could be further evaluated as potential biomarkers. In this study, we attempted to identify a specific lncRNA signature to predict the prognosis of gastric cancer. MATERIAL AND METHODS The genome-wide lncRNA expression in the high-throughput RNA-sequencing data was retrieved from the Cancer Genome Atlas (TCGA). Differential expression of lncRNAs was identified using the Limma package. Survival analysis was conducted by use of univariate and multivariate Cox regression models. Functional enrichment analysis of lncRNAs was based on co-expressed mRNAs. DAVID was used to perform gene ontology and KEGG pathway analysis. RESULTS A total of 452 differentially expressed lncRNAs between gastric cancer and matched normal tissues were screened, of which 76 lncRNAs were identified to be gastric cancer-specific from a pan-cancer analysis of 12 types of human cancer. Among these 76 gastric cancer-specific lncRNAs, 5 lncRNAs (CTD-2616J11.14, RP1-90G24.10, RP11-150O12.3, RP11-1149O23.2, and MLK7-AS1) were significantly associated with the overall survival of patients with gastric cancer. A gastric cancer-specific 5-lncRNA signature was deduced to divide the patients into high- and low-risk groups with significantly different survival times (P<0.0001). Multivariate Cox regression analysis showed that this 5-lncRNA signature was an independent predictor of prognosis. Functional enrichment analysis of the 5 lncRNAs showed that they were mainly involved in DNA replication, mitotic cell cycle, programmed cell death, and RNA splicing. CONCLUSIONS Our results suggest that this tumor-specific lncRNA signature may be clinically useful in the prediction of gastric cancer prognosis.