To investigate the role of HIF-1α genetic polymorphism of c.1772C>T and c.1790G>A in the incidence and prognosis of gliomas in a Chinese cohort, a total of 387 gliomas patients and 437 age- and sex-matched healthy controls were recruited. The genetic polymorphism of c.1772C>T and c.1790G>A was determined. We found that the genotype distribution at c.1772C>T showed significant difference between patients and controls. Multivariable analyses showed a significantly higher risk for gliomas in 1772TT genotype carriers (odds ratio 2.68, with CC as reference). In addition, we also found a significantly higher risk for grade III + IV gliomas was observed in 1772TT genotype carriers (odds ratio 2.21, with CC as reference). The overall survival rates in patients with 1772TT or 1772CT genotype were markedly lower compared with patients with CC (both P < 0.01). Our in vitro studies revealed that HIF-1α regulates the proliferation, migration and invasion of human glioma U251 cells. This study suggests that the c.1772C>T polymorphisms may be used as a molecular marker for gliomas occurrence, grades and clinical outcome in gliomas patients.