Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene–gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. We evaluated the potential implications of the genetic variability of angiotensin converting enzyme (ACE I/D) and angiotensin II type 1 receptor gene (AT1R A1166C) for EH in Uygur population. A case-control study was conducted in 119 hypertensive individuals and 286 individuals with normal blood pressure. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypic distributions of all the polymorphisms satisfied the Hardy-Weinberg proportions in patients and controls. Statistical significance was observed in the genotype (p=0.02) and allele (p=0.06) distributions of AT1R A1166C polymorphism. Logistic regression analysis indicated that the AT1R 1166C allele carriers were positively associated with EH in females (odds ratio (OR) for AC/CC, 3.4; 95% confidence interval (CI), 1.48-7.80, P=0.004). In analysis of gene–gene interaction, we found that there was a significant interaction between the AT1R 1166C and ACE D alleles (P=0.004). OR for EH was significantly higher in 1166C allele carriers with ACE D allele (OR, 2.62; 95% CI,1.37-5.03, P=0.004). A significant interaction between the AT1R 1166C and the ACE D alleles may contribute to the predisposing effect for the development of EH in Uygur population.