Objective To explore the efficacy and short-term prognosis of serum IL-18 in the evaluation of artificial liver in the treatment of HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 151 patients with HBV-ACLF who were treated in our hospital were selected. All patients were successfully treated with artificial liver. According to the outcome within 90 d, the patients were divided into death group and survival group. 73 healthy subjects were selected as controls (healthy group). The serum IL-18 levels of patients before and after treatment and healthy subjects were detected, and the prognostic value of IL-18 level was analyzed. Results The serum IL-18 of HBV-ACLF patients upon admission and after treatment was significantly higher than that of the healthy group, and the serum IL-18 of the death group upon admission and after treatment was significantly higher than that of the survival group (P＜0.05). Spearman correlation analysis showed that IL-18 was positively correlated with MELD. Multivariate Cox regression analysis showed that serum IL-18 level was an independent risk factor for death in patients with HBV-ACLF after artificial liver treatment (P＜0.05). The receiver operating curve (ROC) showed that the area under the curve of serum IL-18 level at admission and after treatment for diagnosing the 90d mortality of HBV-ACLF patients after artificial liver treatment was 0.760 and 0.739, respectively. Kaplan-Meier curve analysis showed that the survival rate of patients with low IL-18 level was significantly higher than that of patients with high IL-18 level (P＜0.05). Conclusion Serum IL-18 can assist in evaluating the therapeutic effect of