Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that belongs to the TNF-ligand superfamily. Objective: To evaluate the ability of urinary TWEAK (uTWEAK) to diagnose lupus nephritis (LN) and its correlation with activity and chronicity index. Patients and Methods: This study was carried out on 75 individuals, 50 SLE patients, fulfilling the SLICC revision of the ACR classification criteria for SLE and 25 age and sex matched apparently healthy control subjects. Patients were assessed by SLE disease activity index (SLEDAI-2K) score. Renal biopsy were done for SLE patients who have confirmed proteinuria >0.5 g in 24-hour urine samples or active urinary sediment or inexplicable decrease in renal function. Urinary TWEAK levels were measured by ELISA. Results: uTWEAK level showed a highly statistical significant difference among groups (P<0.001). There was direct highly significant correlations between uTWEAK and total (t)SLEDAI (r=0.58, P< 0.001) and renal (r)SLEDAI (r=0.73, P<0.001). uTWEAK had significant association with the presence of proliferative GN (Class III, IV) (p= 0.003). At cutoff point ≥ 9.9 pg/mg Cr, uTWEAK had sensitivity of 76% and a specificity of 60 % to diagnose SLE patients with nephritis. At cutoff point of ≤ 14.9 pg/mg Cr, the uTWEAK level had a sensitivity of 88% and a specificity of 76% to predict good response to treatment in LN patients. Conclusion: We concluded that uTWEAK is a candidate biomarker for evaluating LN. It possesses numerous properties that make it suitable for assessment of LN activity and prognosis