We sought to study the clinical efficacy of various combined blood purification techniques in patients with non-viral acute liver failure complicated by multiple organ dysfunction syndrome (MODS). For this purpose, 19 patients diagnosed of mid- or late-stage liver failure with MODS score-4 were randomly divided into 3 treatment groups of PE+HP+CVVHDF, PE+CVVHDF, and HP+CVVHDF, respectively. Pre- and post-treatment heart rate (HR), mean arterial pressure (MAP), arterial blood gases (pH, PaO2, and PaCO2), hepatic function, platelet count, and blood coagulation were determined. The data show significant improvement in HR, MAP, PaO2/FiO2, total bilirubin (TBIL), and alanine aminotransferase (ALT) levels after treatment (P < 0.05). TBIL decreased more significantly after treatment in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.01). Significant improvement in prothrombin time and albumin was observed only in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.05). The decrease of TBIL and improvement of PaO2/FiO2 ratio were more pronounced in PE+HP+CVVHDF than in HP+CVVHDF group (P < 0.05). To conclude, liver function was relatively improved by all the three combined blood purification techniques used; however, PE+HP+CVVHDF approach was found more efficient in the removal of toxic metabolites, especially bilirubin. The data suggest that the combined blood purification techniques used were effective and involved minor side effects.