Objective To explore the effects of different sealing methods in the treatment of liver failure patients using a dual plasma molecular adsorption system combined with plasma exchange. Methods A total of 120 patients with liver failure admitted between January 2022 and October 2024 were enrolled in the study and randomly divided into an observation group and a control group， each consisting of 60 patients. Both groups received treatment with a dual plasma molecular adsorption system combined with plasma exchange. The control group was administered heparin sodium for catheter sealing， whereas the observation group received protamine prior to heparin sodium catheter sealing. The study compared the two groups in terms of liver function indicators—including aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and bilirubin—coagulation function indicators such as fibrinogen and international normalized ratio （INR）， hemoglobin （HGB） levels， catheter blockage rates， and the incidence of adverse reactions. Results No statistically significant differences were observed in liver function， coagulation function， or routine blood parameters between the two patient groups following treatment （P > 0.05）. However， the incidence of blockage in the observation group （3.33%） was significantly lower than that in the control group （20.00%）， with the difference being statistically significant （P < 0.05）. Additionally， no significant differences were found in the occurrence of adverse reactions between the two groups （P > 0.05）. Conclusions The treatment of liver failure involves the use of a dual plasma molecular adsorption system combined with plasma exchange. Administering protamine prior to heparin sodium sealing has minimal impact on the patient's liver function， blood parameters， coagulation profile， and incidence of adverse reactions， yet it effectively reduces the risk of circuit clotting.