Objective To explore the characteristics of serum IL-18 levels in first-episode drugnaive adolescent schizophrenia（ FEDNAS） patients and their correlation with clinical symptoms， so as to assess the potential of IL-18 to predict disease risk. Methods This study was a cross-sectional study. From September 2021 to June 2024， 99 patients with FEDNAS were recruited at the Fourth People's Hospital of Lianyungang， Kangda College of Nanjing Medical University to form the patient group. Concurrently，40 healthy controls matched for age and gender， assessed as having no history of psychiatric disorders， were recruited locally to form the control group. Serum IL-18 concentrations were measured in all subjects. The Positive and Negative Symptom Scale（ PANSS） was used to assess patients' clinical symptoms. The correlation between IL-18 levels and the symptom severity and duration of schizophrenia was analyzed. t-test， χ2 test， analysis of covariance， and Pearson/Spearman correlation analysis were used to evaluate betweengroup differences and variable correlations. Multiple linear regression was used to analyze the correlation between IL-18 and cognitive symptoms. Relative risk was calculated using modified Poisson regression， and attributable fractions and population attributable fractions were also computed. Results Eleven patients（ 11.11%，11/99） in patient group had a family history of mental illness. The total PANSS score of the patient was（ 80.65±15.85）. The serum IL-18 concentration in patient group（ 157.85±55.39） pg/ml was statistically lower than that in control group（ 194.07±62.57） pg/ml（ F=12.952，P ＜ 0.001， Cohen's d=0.63）. The level of IL-18 in FEDNAS patients was negatively correlated with PANSS cognitive factor score（ r= -0.357， P ＜ 0.001）， and positively correlated with disease duration（ rs=0.235，P=0.019）， with statistical differences. The IL-18 level in patients with a disease course of ＜ 2 years was statistically lower than that in control group（ F=7.905，P=0.001）. Based on the results of univariate analysis， all participants' IL-18 levels were divided into a high-expression group（ above the 67% quantile） and a low-expression group（ below the 67% quantile） according to the 67% quantile. Modified Poisson regression analysis revealed that low IL- 18 expression was statistically associated with the risk of FEDNAS［ RR=0.989， 95%CI（ 0.986，0.991）， P ＜ 0.001］. The attributable fraction（ AF） calculations indicated that low IL-18 expression reduced the individual risk of disease onset by approximately 1.11%， with a population attributable fraction（ PAF） of -0.74%. Conclusions Serum IL-18 levels in FEDNAS patients are lower than those in healthy controls， exhibiting a negative correlation with cognitive symptoms and showing pronounced changes in the early disease stage（ ＜2 years）. This suggests that decreased IL-18 levels may reflect an immune response pattern specific to the early disease stage and participate in the pathological process of cognitive impairment in FEDNAS.