Objective  To evaluate the application effects of different priming schemes in the treatment of double plasma molecular absorption system (DPMAS).  Methods  A total of 99 patients with liver failure who underwent DPMAS treatment at Beijing You'an Hospital affiliated to Capital Medical University from September 2024 to September 2025 were recruited for this study. The patients were randomly divided into a basic group, a bubble canister group, and a bubble canister + static group, with 33 patients in each group. Heparin dosage, coagulation grade in post-treatment plasma separator and tubing, incidence of adverse reactions, insoluble particle detection in priming solution, and doctor-nurse satisfaction rate were compared among the three groups undergoing DPMAS treatment.  Results  There were no statistically significant differences in heparin dosage, coagulation grade in post-treatment plasma separator and tubing among the three groups (F=0.703, P=0.497; χ2=0.457, P=0.988). There were no statistically significant differences in adverse reaction rates, including perioral numbness (χ2= 0.471, P=0.790), hypotension (χ2=0.612, P=0.731) and catheter site bleeding (P=1.000). The mean value of insoluble particles detected in the priming solution met the requirements. The satisfaction rates of medical staff were 100%, 6.06% and 0%, respectively, with statistically significant differences among the 3 groups (P＜0.001).  Conclusion  The basic group scheme does not increase the risk of adverse reactions in patients and can achieve effective priming. In addition to the low operational complexity, short priming time, reduced drug use, and decreased nursing workload in basic group, it is highly satisfactory among medical staff. This method is worthy of clinical promotion.