Objective To investigate the value of Chinese group on the study of severe hepatitis B⁃cute on chronic liver failure（COSSH⁃ACLF）score combined with serum interleukin⁃37（IL⁃37）in predicting the short⁃term prognosis of patients with hepatitis B virus infection associated with hepatitis B ⁃ related acute ⁃on ⁃chronic liver failure（HBV⁃ACLF）. Methods From January 2018 to June 2020，129 cases of HBV⁃ACLF patients（HBV⁃ACLF group），53 cases of chronic hepatitis B virus infection（CHB group）and 50 healthy volunteers（control group） were selected from the outpatient department of gastroenterology of our hospital.The COSSH ⁃ACLF score was calculated，detected the serum level of IL⁃37，alanine aminotransferase（ALT），aspartate aminotransferase（AST）， total bilirubin（TBIL），albumin（Alb）and cholinesterase（CHE）. The clinical data of the HBV⁃ACLF group and the clinical outcomes on admission for 30 days were collected. According to the clinical outcomes，the patients were divided into death group（35 cases）and survival group（94 cases）.Logistic regression analysis was conducted for the risk factors of death in patients with HBV ⁃ACLF. ROC analysis was conducted for the value of COSSH ⁃ ACLF score combined with IL ⁃ 37 in predicting the short ⁃ term prognosis of patients with HBV ⁃ ACLF. Results COSSH ⁃ACLF score，serum IL ⁃37，ALT，AST and TBIL level in HBV ⁃ACLF group were higher than those in CHB group and control group（P < 0.05），while CHE and Alb were lower than those in CHB group and control group （P < 0.05）. Logistic regression analysis showed that complicated with hepatic encephalopathy，low HBV ⁃DNA， high COSSH ⁃ACLF score，and high IL ⁃37 were risk factors affecting the prognosis of patients with HBV ⁃ACLF （P < 0.01）. ROC analysis results showed that the area under the curve（AUC）of COSSH⁃ACLF score combined with IL ⁃37 predicted the prognosis of patients with HBV ⁃ACLF was 0.880、0.798、0.954，and the sensitivity and specificity were 82.86%，71.43%，91.43%；85.11%，76.60%，94.68%. Conclusion COSSH⁃ACLF score and serum IL⁃37 level in patients with HBV⁃ACLF are significantly increased，COSSH⁃ACLF score and IL⁃37 are related to the short⁃term prognosis of patients with HBV⁃ACLF，and COSSH⁃ACLF score combined with IL⁃37 can improve the accuracy of short⁃term prognosis prediction of HBV⁃ACLF.