Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure (BP). The aldosterone-synthase gene (CYP11B2) has been regarded as a candidate gene for essential hypertension. To address this issue, we carried out a haplotype-based, case-control study to explore the association between a human CYP11B2 gene and essential hypertension (EH) in the southwest Han population of China (n = 1020 individuals). Four tag single-nucleotide polymorphisms (SNPs) (rs4536, rs4545, rs3097, and rs3802230) and the C-344T polymorphism, as well as the K173R polymorphism in the CYP11B2 gene, were genotyped using the PCR-RFLP method. Single-locus analysis showed that the C allele of rs3802230 was significantly more prevalent in the EH subjects as compared to control subjects, adjusted for covariates. Haplotype analysis showed that the haplotype AAGC constructed by the tag SNPs (rs4536, rs4545, rs3097, and rs3802230), which carried the susceptible rs3802230 C allele, significantly increased the risk of essential hypertension with an odds ratios equal to 3.56 (P = 0.0001). The present results indicated that the rs3802230 C allele might be a risk marker for essential hypertension and haplotype AAGC might confer high genetic susceptibility to essential hypertension in a southwest Han Chinese population.