To verify the accuracy of the model for end-stage liver disease-sodium (MELD-Na), chronic liver failure consortium organ failure score (CLIF-C OFs), Chinese Group on the Study of Severe Hepatitis B-Acute-on-chronic Liver Failure score (COSSH-ACLFs) and neutrophil-to-lymphocyte ratio (NLR) scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and to explore its value in clinical application. The clinical data (gender, age, disease stage) and laboratory indicators [alanine transferase (ALT), glutamate transaminase (AST), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), serum sodium (Na), prothrombin activity (PTA), international standardized ratio (INR), neutrophils count (NEU) and lymphocytes count (LYM)] of 163 patients with HBV-ACLF from July 2010 to July 2018 in Tianjin Second People's Hospital were retrospectively analyzed. After 8 weeks of admission, the patients were divided into death group (90 cases) and survival group (73 cases) according to survival status. The MELD-Na, CLIF-C OFs, COSSH-ACLFs scores and NLR of death group and survival group were compared, and a multivariate Logistic regression analysis was used to analyze the independent risk factors for HBV-ACLF. Propensity score analysis was used to demonstrate the accuracy of the method and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the independent risk factors. There were no significant differences in gender, disease stage, ALB, BUN, Cr, Na, NEU on admission between the two groups (all P > 0.05). The age [years old: 43.00 (34.00, 53.00) vs. 50.00 (42.50, 55.00)] and serum levels of ALT [U/L: 252.90 (61.43, 613.33) vs. 359.10 (115.15, 784.70)], AST [U/L: 146.15 (90.88, 449.30) vs. 237.80 (109.00, 635.05)], TBil [μmol/L: 265.10 (183.10, 347.60) vs. 307.50 (229.90, 405.55)] and INR [2.13 (1.91, 2.46) vs. 2.29 (2.02, 2.94)] in survival group were lower than those in death group and the PTA [%: 34.00 (28.00, 38.00) vs. 31.00 (24.00, 36.00)] and LYM [×109/L: 1.37 (0.72, 1.79) vs. 0.85 (0.51, 1.39)] levels were significantly higher than those in death group (both P < 0.05). The MELD-Na [17.99 (16.60, 19.63) vs. 19.16 (17.43, 20.80)], CLIF-C OFs [9.00 (8.00, 9.00) vs. 9.00 (9.00, 10.00)], COSSH-ACLFs [4.87 (4.63, 5.48) vs. 5.47 (5.07, 5.80)] and NLR [2.86 (2.21, 5.19) vs. 4.38 (2.54, 8.46)] were lower in survival group than those of the death group (all P < 0.05). Logistic regression analysis showed that CLIF-C OFs [odds ratio (OR) = 0.532, 95% confidence interval (95%CI) was 0.380-0.744, P < 0.05] and NLR (OR = 0.901, 95%CI was 0.835-0.972, P < 0.05) were the independent risk factors for the prognosis of HBV-ACLF. After propensity score matching, the data of 59 cases in each group were successfully matched, there were no significant differences in age, gender, disease stage, ALT, AST, TBil, ALB, BUN, Cr, Na, PTA, INR and NEU between the two groups (all P > 0.05), and statistically significant difference in the baseline LYM [×109/L: 1.35 (0.74, 1.73) vs. 0.81 (0.51, 1.30)] were found between the survival group and the death group. The CLIF-C OFs, COSSH-ACLFs scores and NLR were lower in survival group compared with those of the death group [CLIF-C OFs: 9.00 (8.00, 9.00) vs. 9.00 (8.00, 10.00), COSSH-ACLFs: 4.99 (4.69, 5.64) vs. 5.34 (5.03, 5.81), NLR: 2.85 (2.21, 5.72) vs. 4.38 (2.47, 10.20), all P < 0.05] and CLIF-C OFs (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) and NLR (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) were still as the independent risk factors for the prognosis of HBV-ACLF. The sensitivity of CLIF-C OFs ≥ 9 and NLR ≥ 3.14 to forecast the 8-week clinical outcome of HBV-ACLF patients were 76.7% and 67.1%, the specificity were 48.9% and 56.7%, and AUC were 0.662 and 0.623. CLIF-C OFs was combined with NLR to increase the specificity of forecasting the 8-week clinical outcome of HBV-ACLF patients to 77.8%. CLIF-C OFs and NLR scores are independent risk factors affecting the clinical outcome of HBV-ACLF, and have better clinical value in predicting the prognosis of HBV-ACLF. Combined application of the two scores will be more beneficial to the prognosis of HBV-ACLF.