Studies on HIF 1α C1772T (P582S) polymorphism revealed a genetic susceptibility to malignant tumors, however, the results were conflicting. We conducted a meta-analysis utilizing 29 eligible case-control studies to analyze the data concerning the association between the HIF-1α C1772T polymorphism and cancer risks. There was statistical association between the HIF-1α CT/TT genotype and cancer risk (OR = 1.28, 95% CI = 1.06-1.54, P(heterogeneity) < .00001). The stability of these observations was confirmed by a one-way sensitivity analysis. Our findings suggested that CT/TT genotype was associated with increased risks of prostate cancer. Besides, the HIF-1α C1772T polymorphism most likely contributes to susceptibility to malignant tumors, especially in American population.