Many studies have suggested that heme oxygenase-1 (HMOX1) might be implicated in blood pressure (BP) regulation. We hypothesized that this gene might be responsible for the variation of susceptibility to essential hypertension (EH) and BP and investigated three polymorphisms in HMOX1 (i.e., the (GT)n repeat in the HMOX1 promoter and single-nucleotide polymorphisms (SNPs) rs2071746 and rs2071749) in population-based samples of 789 Han Chinese from Xinjiang, China. The GT repeat numbers ≥33, 27-32, and <27 in the HMOX1 promoter were defined as long (L), middle (M), and short (S) alleles, respectively. The participants carrying SS or SM genotype were sorted into one group, and the participants carrying SL, MM, ML, or LL genotype were sorted into another group. The (GT)n repeat in the HMOX1 promoter showed significant association with EH and BP, whereas SNPs rs2071746 and rs2071749 did not. Compared with the SS+SM (GT)n group, the MM+SL+ML+LL (GT)n group had a lower risk of EH (adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.82; p = 0.002) and lower systolic (128.3 ± 1.3 vs. 132.2 ± 1.0 mm Hg, adjusted p = 0.014) and diastolic BPs (81.7 ± 0.8 vs. 84.5 ± 0.7 mm Hg, adjusted p = 0.009). These findings provide the first genetic evidence for the role of the (GT)n repeat in the HMOX1 promoter in the susceptibility to human EH and the variation of BP.