Abstract: ob＜x＞jective The characteristics of antidepressant me＜x＞tabolism gene phenotypic polymorphism were analyzed in patients with treatment-resistant depression (TRD) to provide a reference for clinical treatment. Methods Collect the diagnosis and treatment information and pharmacogenomics test results of TRD patients who were treated in Xuzhou Oriental People’s Hospital from September 2018 to May 2020. The gene polymorphism was analyzed, includes CYP1A2(*1,*1C,*1F,*6), CYP2C19(*1,*10,*17,*2,*3,*35,*4), CYP2C9(*1,*2,*3), CYP2D6(*1,*10,*14A,*14B,*2,*2A,*4,*41) and CYP3A4(*1,*20,*26). Results 91.89% of patients with TRD had more than one me＜x＞tabolic gene phenotypic mutation, concentrated in CYP2C19 (59.46%) and CYP2D6 (64.86%), with the most frequent frequency of poor me＜x＞tabolizer. No mutation was found in 8.11% of patients with TRD. Conclusion Chinese Han patients with TRD have a higher rate of phenotypic mutations in me＜x＞tabolic genes, mainly concentrated in CYP2C19 and CYP2D6, with the poor me＜x＞tabolizer frequency being the most frequent. At the same time, we must be alert to the possibility of false treatment-resistance.