Objective：To investigate the safety of albumin combined with acetate Ringer’s solution in therapeutic plasma exchange （TPE）of pediatrics. Methods：A total of 20 patients with diseases requiring TPE from April 2019 to March 2023 in the intensive care unit of the Affiliated Children’s Hospital of Nanjing Medical University were included，and were randomly divided into an observation group and a control group. The observation group chose 20% albumin combined with acetate Ringer’s solution in the ratio of 1∶5 as the replacement fluid，and the control group chose fresh frozen plasma as the replacement fluid for TPE. The hemodynamic indexes，the occurrence of complications during treatment，the coagulation indexes，biochemical indexes and the response of the underlying disease 1 week after the end of treatment between the 2 groups of patients were compared. The coagulation indexes and biochemical indexes were compared within groups before and after TPE. Results：Mean arterial pressure and heart rate were stable in both groups during treatment without significant differences（P＞0.05）. Total protein（TP），globulin（GLB），fibrinogen（Fbg），serum phosphorus（P）and serum calcium（Ca²⁺ ）decreased after treatment compared with those before treatment in the observation group，and the differences were statistically significant（P＜ 0.05）. Albumin（ALB），international normalized ratio（INR），prothrombin time（PT），P，Ca²⁺ and serum magnesium（Mg²⁺ ）decreased after treatment compared with those before treatment in the control group，and the differences were statistically significant（P＜0.05）. The incidences of allergic metaplasia and hypocalcemia between the two groups after treatment were not statistically significant（P > 0.05）. The coagulation indexes，biochemical indexes and the response of the underlying disease 1 week after the end of treatment between two groups were not statistically significant（P > 0.05）. Conclusion：It is safe to apply 20% albumin combined with acetate Ringer’s solution（1∶5）as the replacement fluid in TPE of pediatric patients and can effectively save blood resources，but the coagulation and biochemical indexes need to be monitored during the treatment，and blood products，such as fresh frozen plasma，should be supplemented promptly to correct coagulation function.