Interleukin-18 (IL-18) is a vital cytokine, which mediated organ failure and elevated in autoimmune disorders as Systemic Lupus Erythematosus. This study investigated the importance role of IL-18 as a diagnostic marker for disease activity of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN). This cross-sectional study was carried out on 41 SLE patients with LN, 31 lupus non-nephritis patients and 20 healthy controls. The IL-18 serum levels were measured by IL-18 ELISA kit, to evaluate the activity of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The results showed significant increase in serum IL-18 level in patients with LN (174.09±33.19) than both lupus non nephritis patients (9139.45±64.39) and healthy control (46.06±16.42), with significant correlation between IL-18 level and SLEDAI.