Abstract: Objective To study the frequency of CYP2 C19*2 polymorphism in Chinese people and the potential effects on adverse reactions during cyclophosphamide treatment in systemic lupus erythematosus (SLE). Methods We studied 324 unrelated Chinese systemic lupus erythematosus patients from Peking Union Medical College Hospital and 319 healthy controls. CYP2 C19*2 polymorphism was genotyped by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), and then verified by sequencing. Further statistical analysis was carried out with clinical data. Results The observed frequency of mutant CYP2 C19*2 polymorphism is 29.9% in Chinese people. A total of 237 patients in the SLE group had been treated with cyclophosphamide, and 163 patients had been treated with cyclophosphamide for more than 6 months. The percentage of leukopenia in CYP2 C19*2 carriers was lower, and no significant correlation was found, while CYP2 C19*2 polymorphism was significantly associated with abnormal liver function and uterine bleeding. Multivariate logistic regression model analysis showed that CYP2 C19*2 polymorphism and cumulative dosage of cyclophosphamide were independent factors for abnormal uterine bleeding. Conclusion CYP2 C19*2 polymorphism is not uncommon in Chinese Han population and it might lower the risk of some toxicity of cyclophosphamide in SLE patients.