Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count. While corticosteroids are a useful first-line therapy for ITP patients, their long-term effectiveness is limited, and the determinants of corticosteroid sensitivity in ITP patients remain largely unknown. Sirtuin 1 (SIRT1), a member of the mammalian sirtuin family, is related to the anti-inflammatory effects of corticosteroids. Here, we investigate the contribution of the SIRT1 single-nucleotide polymorphisms (SNPs) rs12778366 and rs4746720 to ITP susceptibility.We recruited 330 ITP patients and 309 healthy controls from Han population, and performed genotyping of SIRT1 rs12778366 and rs4746720 using a MassARRAY system. The results were validated in another 55 ITP patients from ethnic minorities.Using clinical data of patients and controls from Han polulation, including corticosteroid sensitivity, susceptibility, refractoriness, and severity, our results revealed that the CC/TC genotypes of SIRT1 rs12778366 were associated with a 2.034-fold increased risk of corticosteroid resistance compared to the homozygous major TT genotype (dominant, CC/TC vs. TT, OR = 2.034, 95% CI = 1.039-3.984, p = 0.038). In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a 0.560-fold decreased risk of corticosteroid resistance (dominant, 95% CI = 0.321-0.976, OR = 0.560, p = 0.041). The C allele substitute in SIRT1 rs12778366 was significantly associated with the corticosteroid sensitivity of ITP patients (p = 0.021). The similar results were obtained in minority ITP patients.This study indicates that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.