BACKGROUND: Double plasma molecular adsorption system cannot only specifically absorb bilirubin and bile acids, but also eliminate toxins, inflammatory transmitters and cytokines in the body. In the absence of plasma or in the case of plasma deficiency, it can effectively remove harmful substances, prevent multiple organ failure and fight for time for the liver regeneration and recovery of liver function, which is suitable for liver failure caused by various reasons. OBJECTIVE: To compare the validity and safety of double plasma molecular adsorption system combined with plasma exchange and simple plasma exchange in the treatment of liver failure. METHODS: Sixty patients with liver failure admitted to the Guizhou Provincial People's Hospital from October 2014 to October 2017 were included and randomized into two groups (n=30/group) . Plasmapheresis was used in plasma exchange group, and the volume of plasma exchanged was 2 500-3 000 mL. The combination treatment group was treated by double plasma molecular adsorption system combined with plasma exchange, and the volume of plasma exchanged was 1 000-1 500 mL. In the two groups, the clinical effects and liver function were evaluated after three treatment sessions, and adverse reactions were observed during the artificial liver treatment. RESULTS AND CONCLUSION: After treatment, the levels of serum total bilirubin and alanine aminotransferase were significantly lower than those before treatment, and the prothrombin activity was significantly higher than that before treatment (P < 0.05) . However, the serum albumin level showed no significant difference in the combination treatment group before and after treatment. Compared with the plasma exchange group, the post-treatment levels of serum total bilirubin, alanine aminotransferase and serum albumin were significantly lower in the combination treatment group, and the prothrombin activity was significantly higher (P < 0.05) . (2) The total effective rate of the combination treatment group (83％) was significantly higher than that of the plasma exchange group (63％) (P < 0.05) . (3) During the artificial liver treatment, there was one case of rash, one case of chills and one case of hypotension in the combination group, while no adverse reaction occurred in the plasma exchange group. (4) To conclude, either double plasma molecular adsorption combined with plasma exchange or simple plasma exchange can markedly improve the liver function of patients with liver failure, and produce few adverse reactions. However, the combination of double plasma molecular adsorption and plasma exchange has an advantageous therapeutic effect and can reduce plasma consumption.