Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P = 0.03) and IL-18 (P = 0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P < 0.001, r p = 0.5) is significantly stronger than it is in mild SLE (P < 0.001, r p = 0.4) with similar nonrenal SLEDAI score (P = 0.032, z = 1.85). Between these two serum markers, sFas is the only predictor of proteinuria.