Objective  To observe the clinical effect of different plasma adsorption volume in the treatment of hyperbilirubinemia using the double plasma molecular adsorption system.  Methods  A total of 40 patients with hyperbilirubinemia treated with double plasma molecular adsorption system in the Seventh People's Hospital of Shanghai University of TCM were enrolled in this study. According to the plasma adsorption volume in a single treatment they were divided into groups. Blood routine, coagulation function, C-reactive protein, bilirubin clearance rate and others were compared among groups.  Results  A total of 60 times of double plasma molecular adsorption treatment were performed in the 40 patients, in which 4 times of the treatment were significant effective, 50 times were effective, and 6 times was ineffective, with the total effective rate of 90%. After the treatment, the reduction rate of bilirubin was more significant in the patients using plasma adsorption volume of 1.0～1.4L (group C) or 1.8～2.2L (group E) in a single treatment than in the patients using plasma adsorption volume of 0.6～1.0L (group B) (t=-2.403 and -2.405, P=0.023 and 0.032), and was more significant in group C than in group B (t=-2.068, P=0.048). After the treatment, prothrombin time and activated partial thromboplastin time prolonged (t=-3.662 and -2.828, P=0.001 and 0.008), the international normalized ratio increased (t=-3.092, P=0.004), and plasma fibrinogen (t=4.786, P<0.001), platelet count     (t=4.963, P<0.001) and C-reactive protein decreased (t=3.088, P=0.004).  Conclusion  The double plasma molecular adsorption system reaches the maximum clearance of bilirubin when the plasma adsorption volume ranges between 1.0 to 1.4 L in a single treatment. The efficient of bilirubin clearance can be further increased if the treatment time in the adsorption column is prolonged. It is recommended that the suitable plasma adsorption volume in a single treatment is 3.5～5.5 times of the plasma volume in a patient.