Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by various aberrations including increased production of IL-18. As IL-18 105 A>C polymorphic variants have been linked to increased production of this cytokine, we investigated the prevalence of IL-18 105 A>C (rs549908) polymorphic variants in SLE patients (n = 111) and controls (n = 152). There were no significant differences in the distribution of IL-18 105 A>C polymorphic variants in SLE patients and controls. However, there was a significant association between the IL-18 105 AA genotype (recessive model) and renal manifestations OR = 3.360 (1.523–7.415, P = 0.0039) and the P value remained statistically significant after Bonferroni correction (P corr = 0.0351).Our findings indicate that the IL-18 105 AA genotype variant can contribute to renal manifestations in patients with SLE.