Artificial liver support systems (ALSSs) have been recommended as important approaches for treating liver fuilure (LF) patients. However, very few studies have focused on the screening of potential serum therapeutic markers of LF patients treated by ALSSs. Here, serum samples were obtained from 57 LF patients before and after ALSSs treatment and analyzed by metabonomics. The results showed that ratios of creatine:creatinine, taurine:creatinine, and lactate:creatinine were significantly altered and restored to normal levels after ALSSs treatment. The ratio of lactate:creatinine showed the highest area under a receiver-operating characteristic curve (AUROC) value (0.650), which was higher than that of the prothrombin time activity (PTA, 0.562). A retrospective analysis showed that serum lactate:creatinine ratios among the LF patient groups were 0.038 ± 0.002 (survival group, n=48), 0.048 ± 0.005 (three-month death group, n=24), and 0.052 ± 0.005 (one-month death group, n=33), which was significantly negatively correlated with survival (r= - 0.26). Another retrospective cohort analysis (n=81) of LF patients showed that the lactate-creatinine ratio in the death group remained unchanged, but fell markedly in the survival group (0.052 ± 0.005 vs. 0.025 ± 0.002) after ALSSs treatment. In comparison, the serum PTA levels were no statistical differences of in both the death group and survival group after ALSSs treatment. The AUROC of serum lactate-creatinine ratio and PTA after ALSSs treatment for diagnosis of survival group from death group was 0.682 and 0.591 respectively. These results indicate that the serum lactate-creatinine ratio may be more reliable than measures of PTA to evaluate the therapeutic effect of ALSSs treatment in LF patients.