The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual's susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06-2.72), particularly among older patients (OR=2.01; 95%CI=1.05-3.86), smokers (OR=2.06; 95%CI=1.07-3.99), never drinkers (OR=2.16; 95%CI=1.20-3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02-2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22-3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23-3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.