Tumors are usually characterized by an imbalance in cytosine methylation, including hypomethylation of CpG islands. In this study, bisulfite sequencing PCR was used to assess the promoter methylation status of coagulation factor X (F10) gene in tumors of 96 glioma patients and in glioma cells U251, SF767, and SF126, and the effect of promoter hypomethylation on protein expression was evaluated immunohistochemically. The study showed that the demethylation ratio of F10 in SF126, SF767, and U251 cells was 38.6, 26.4, and 24.3% respectively. Hypomethylation of F10 was detected in 82.3% of glioma specimens and in no normal brain tissues, with significant correlation with its protein expression. However there was no remarkable relationship between F10 hypomethylation and sex, age, and advanced tumor grade. The correlation between F10 hypomethylation, protein expression, and overall survival (OS) was statistically significant. Hypomethylation of F10 promoter in gliomas accounted for F10 encoding protein FX overexpression and aggressive biological behavior in a subset of patients. Furthermore, in the F10 hypomethylation group, OS was shorter for patients with F10 overexpression than for those without. Detection of these epigenetic changes in tumors may provide important information regarding prognosis.