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OBJECTIVES Dysregulated DNA methylation is common in cancers and is considered one of the most important triggers in cancer development and progression. The expression and promoter methylation status of long non-coding RNA (lncRNA) H19 play a key role in several cancers, but its role is unclear in oral cancer. The aim of this study was to evaluate the potential of lncRNA H19 as a prognostic biomarker for oral cancer. DESIGNS The transcript levels and the methylation status of lncRNA H19 in OSCC cell lines and OSCC patient tissues were investigated by quantitative real-time RT-PCR (qRT-PCR) and methylation-specific PCR (MSP). Methylation ratio (%) were calculated from the intensity of the MSP in the gel image and Kaplan-Meier survival analysis of OSCC patient survival was performed for patients grouped according to the lncRNA H19 promoter methylation ratio. RESULTS lncRNA H19 was highly expressed and its promoter region was hypomethylated in OSSC cell lines as compared to normal control. Almost all OSCC patients tissues (63 out of 65, 97 %) showed hypomethylation of lncRNA H19 compared to normal oral mucosa tissues. There was a significant correlation between methylation ratio and tumor histopathologic grade. OSCC patients with hypomethylation of lncRNA H19 had a significantly lower 5-year survival rate. CONCLUSIONS Hypomethylation of lncRNA H19 may serve as a potential prognostic biomarker for oral cancer.