Background: Non-thyroidal illness syndrome (NTIS) develops in a large proportion of critically ill patients and is associated with high risk for death. We aimed to investigate the correlation between NTIS and liver failure,and the short-term mortality of patients with these conditions.Methods: The clinical data of 87 patients with liver failure were collected retrospectively,73 of them were randomly selected for an observational study and to establish prognostic models,and 14 for model vali-dation. Another 73 sex-and age-matched patients with mild chronic hepatitis were randomly selected as a control group. Serum free triiodothyronine (FT3),free thyroxine (FT4),and thyroid-stimulating hormone (TSH) were measured. The clinical characteristics of patients with liver failure and NTIS were analyzed. The follow-up of patients lasted for 3 months. Additionally,the values for predicting short-term mortal-ity of model for end-stage liver disease (MELD),Child-Turcotte-Pugh (CTP),chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores,FT3-MELD model,and FT3 were evaluated. Results: The observation group had significantly lower FT3 (2.79 ± 0.71 vs. 4.43 ± 0.75 pmol/L,P < 0.001) and TSH [0.618 (0.186-1.185) vs. 1.800 (1.570-2.590) mIU/L,P < 0.001],and higher FT4 (19.51 ± 6.26 vs. 14.47 ± 2.19 pmol/L,P < 0.001) than the control group. NTIS was diagnosed in 49 of the patients with liver failure (67.12％). In the observation group,patients with NTIS had a higher mortality rate than those without (63.27％ vs. 25.00％,P = 0.002). Across the whole cohort,the 3-month mortality was 50.68％. The international normalized ratios (INR) were 2.40 ± 1.41 in survivors and 3.53 ± 1.81 in deaths ( P = 0.004),the creatinine (Cr) concentrations were 73.27 ± 36.94 μmol/L and 117.08 ± 87.98 μmol/L ( P = 0.008),the FT3 concentrations were 3.13 ± 0.59 pmol/L and 2.47 ± 0.68 pmol/L ( P < 0.001),the MELD scores were 22.19 ± 6.64 and 29.57 ± 7.99 ( P < 0.001),the CTP scores were 10.67 ± 1.53 and 11.78 ± 1.25 ( P = 0.001),and the CLIF-SOFA scores were 8.42 ± 1.68 and 10.16 ± 2.03 ( P < 0.001),respectively. FT3 was negatively correlated with MELD score ( r = ? 0.430,P < 0.001). An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula: Logit( P ) = ? 1.337 × FT3 + 0.114 × MELD + 0.880. The area under the receiver operating characteristic (ROC) curve was 0.827 and the optimal cut-off value was 0.4523. The corresponding sensitivity and specificity were 67.6％ and 91.7％. The areas under the ROC curve for FT3 concentration,MELD score,CTP score,and CLIF-SOFA score were 0.809,0.779,0.699,and 0.737,respectively. Conclusions: Patients with liver failure often develop NTIS. FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure. Thus,the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.