Aims: Based on a large sample size, this study aims to analyze the genetic and phenotypic frequency distributions of CYP2C19, CYP2B6, and CYP2D6 in the Chinese Han population, providing valuable references for individualized psychotropic drug therapy. Methods: A retrospective analysis was conducted on genetic data from over 6,000 psychiatric patients tested for psychotropic drug-related genetic polymorphisms between March 2021 and August 2024 at the First Hospital of Hebei Medical University. Genetic polymorphisms in CYP2C19, CYP2B6, and CYP2D6 were analyzed using Agena MassARRAY Assay. Additionally, CYP2D6 copy number variations(CNVs) were quantified using the TaqMan real-time qPCR assay. Results: The sample sizes were 6,964 for CYP2D6, 6,681 for CYP2C19, and 5,712 for CYP2B6, all from the Han Chinese population. The most common allele variants were CYP2C19*2 (30.15%), CYP2D6*10 (66.20%), and CYP2B6*6 (16.25%). The predominant genotype mutations were CYP2C19 *1/*2 (36.85%), CYP2D6 *1/*10 (24.64%), and CYP2B6 *1/*6 (23.62%). The predominant phenotypes were intermediate metabolizer for CYP2C19 (44.23%), normal metabolizer for CYP2D6 (60.20%), and normal metabolizer for CYP2B6 (57.95%). The CNVs for CYP2D6 were as follows: 0.47% for zero copies, 13.96% for one copy, 83.49% for two copies, and 2.08% for three or more copies. Conclusions: Our data complemented the pharmacogenomic information of the Han Chinese population, providing a theoretical basis for personalized treatment of variant carriers. Physicians should refer to preemptive Pharmacogenomics(PGx) test results for appropriate dose adjustments in accordance with guidelines.