Abstract Interleukin-2 (IL-2), one of the crucial immunoregulatory cytokines required for T lymphocyte activation, plays an important role in autoimmune diseases. An IL-2 genetic G/T polymorphism (rs2069763) has been linked with multiple sclerosis and rheumatoid arthritis. We tested a hypothesis that this polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Han Chinese SLE patients and a healthy control group in Taiwan. Our results indicate (a) a significantly higher G allele frequency in SLE patients (P=1.91×10?14; OR=3.94; 95% CI=2.74–5.66), (b) a significantly higher G allele frequency in SLE patients with antinuclear antibodies (ANA) (P=0.033; OR=4.21; 95% CI=1.01–17.51) and (c) a significantly lower G allele frequency in SLE patients with discoid rash (P=0.019; OR=0.41; 95% CI=0.19–0.88). Our results suggest that this polymorphism may be involved in the genetic background of Taiwanese SLE.