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Idiopathic nephrotic syndrome (NS) is a common glomerular disease in children throughout the world; however, the exact pathogenesis of the disease remains unknown. Several studies have shown that tumour necrosis factor-alpha (TNF-α), a proinflammatory cytokine, plays a significant role in the pathogenesis of NS. The literature lacks sufficient data to establish the relationship between TNF-α and NS. This prospective study was conducted on children aged 1–14 years diagnosed with idiopathic NS. All enrolled individuals were followed up from disease onset or relapse of NS until remission or at least 42 days with steroid therapy if remission was not achieved. Serum TNF-α levels were measured at presentation and remission or after 42 days of steroid therapy if remission was not achieved. The role of TNF-α levels in response to steroid therapy in NS was also assessed. One hundred and twelve children (68% boys) with idiopathic NS were enrolled. The median age (interquartile range) at enrolment was 58.5 (37–84.7) months, while the median age at symptom onset was 47.5 (24–60.7) months. The median TNF-α level at presentation was 7.5 (3.5–12.1) pg/ml, and that at remission was 5.25 (1.62–8.8) pg/ml. The median TNF-α levels among first-episode NS at presentation were 3.98 pg/ml and 1.88 pg/ml (P  = .04) at remission, whereas in steroid-resistant NS, it was 6.59 pg/ml at presentation and 9.02 pg/ml at 42 days (P  = .45). There was a significant negative correlation between the duration of steroid therapy and TNF-α levels, with a correlation factor of −0.021 and R 2 of 0.154 (P ≤.001). Serum TNF-α levels decrease with steroid therapy in children with steroid-sensitive NS, which correlates clinically with the achievement of remission. [ABSTRACT FROM AUTHOR]