The molecular mechanisms underlying essential hypertension are not fully elucidated. Although Benazepril is being widely used in antihypertensive medication, the agent is efficacious in only a portion of hypertensive patients. To evaluate the interaction of alpha-adducin gene Gly460Trp and angiotensin I-converting enzyme (ACE) gene I/D polymorphisms in regard to baseline blood pressure (BP) levels and the reductions of blood pressures after Benazepril treatment, we conducted an investigation of 954 Chinese hypertensive patients in Anhui province, China. We found that compared with the baseline systolic BP (SBP) of subjects with one ACE I allele and one alpha-adducin Trp allele, the baseline SBP of those with ACE DD and alpha-adducin Gly/Gly genotypes was significantly higher [Crude: beta(SE) = 7.83(3.09), p = .01; Adjusted: beta(SE) = 5.83(2.83), p = .04]. However, no associations were found between the interaction of ACE I/D and alpha-adducin Gly460Trp polymorphisms and the baseline diastolic BP or the BP response to Benazepril treatment. Our results suggested that the interaction effect of alpha-adducin Gly460Trp and ACE I/D polymorphisms might play a significant role in regulating baseline BP but not BP response to Benazepril.