Introduction Cytochrome P450 (CYP) is a key monooxygenase superfamily mediating the elimination of anti-hypertensive drugs. Genetic polymorphisms of CYP would lead to differential drug efficacy. Building relationships between genotype–phenotype will benefit individual medical treatment of hypertension. Areas covered The review systematically summarizes the polymorphisms of four CYPs (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) concentrated distributed in the Han Chinese population. Moreover, the activities of variants on metabolizing anti-hypertensive drugs are reviewed, especially drugs with adrenoceptor blocking properties. Moreover, their clinical relevancies were discussed. Expert opinion The polymorphisms of CYP can cause fluctuation in drug exposure of antihypertensive drugs. Although the clinical relevance between them has been built partially, the translational medicine still lacks reliable data support. Furthermore, the studies have demonstrated that even the same CYP variant will show different catalytic characteristics for different drugs, which is another obstacle to hinder its application in clinic. With the deepening of multiomics research and structural biology, nucleotide polymorphisms can be combined with transcriptome, proteome, metabolome and molecular structure analyses to study the relationship among susceptibility to hypertension and drug efficacy. A complete “genotype–protein structure–phenotype–dose” chain can be established and strengthened by combining studies of pharmacokinetics-pharmacodynamics, which can effectively promote the precise application of anti-hypertensive drugs.