Objective: Prolylcarboxypeptidase (PRCP) is a negative regulator of the pressor actions of the renin-angiotensin-aldosterone system. It is also involved in the kallikrein-kinin system. This gene has an important role in blood pressure (BP) regulation. Methods: A case-control study was performed for 615 Yi participants (303 cases and 312 controls) from a remote mountainous area in Yunnan Province of China. For the PRCP gene, 11 tag single-nucleotide polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The PRCP gene rs12290550 was associated with the occurrence of essential hypertension (EH) and BP traits. Logistic regression analysis indicated that the rs12290550 T allele was significantly linked to the risk of EH (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.44-2.39, p = 0.2 x 10(-5)). Under Bonferroni correction, the H7 TAGCACTAACA haplotype containing the risk allele rs12290550 T increased the risk of EH (OR = 4.53, 95% CI 2.29-8.93, p = 0.2x10(-5)). Conclusions: The findings of this study demonstrate the strong association of the PRCP gene with EH. rs12290550 may be a useful genetic predictor of EH in the Yi minority.