Objective: To assess humanistic care nursing mode for severe hyperbilirubinemia patients who undergoing double plasma molecular adsorption system and plasma exchange. Methods: 124 participants were diagnosed with severe hyperbilirubinemia and were received combined treatment, include that double plasma molecular adsorption system and Plasma exchange. They were randomly assigned to control group (n = 62) and intervention group (n = 62). We collect the participant information by Self-Rating Anxiety Scale, Self-rating depression scale and the Short Form-36. The information include the satisfaction of patients, anxiety status, depression status and quality of life. Result: In patient satisfaction research, the intervention group has more very good level assessment than that of control group (41 vs 32). Also, control group has more good level assessment than that of intervention group (18 vs 8). In anxiety and depression research, intervention group has better improvement in anxiety status, it is from 56.4±6.7 to 45.3±5.1. In quality of life research, the intervention group has greater improvement than that of control group in every domain. Conclusion: humanistic care nursing mode provide better improvement in mental health aspect of patient. It significantly improved anxiety and depression, and improved overall quality of life after treatment.