Objective To study the clinical features, treatment, and prognosis of pure red cell aplasia (PRCA) in children. Methods A retrospective analysis was performed for the clinical data of 16 children with PRCA. The outcome and prognosis of patients treated with prednisone combined with Huaiqihuang granules versus prednisone alone were evaluated. Results All the 16 children complained of symptoms of anemia including pale or sallow complexion. Of 12 children undergoing pathogen test, 7 (58%) were found to have pathogen infection, among which human cytomegalovirus was the most common. Lymphocyte subsets were measured for 7 children, among whom 5 (71%) had lymphocyte immune disorder. Six children were found to have abnormalities in immunoglobulin and complement. The 8 children treated with prednisone combined with Huaiqihuang granules had a median follow-up time of 21.5 months, among whom 1 was almost cured, 1 was relieved, and 6 were obviously improved; the median onset time of treatment was 1 month, and 2 children had disease recurrence in the course of drug reduction or withdrawal. The 8 children in the prednisone alone treatment group had a median follow-up time of 34 months, among whom 4 were almost cured, and 4 were obviously improved; the median onset time of treatment was 2.5 months, and 4 children had recurrence during drug reduction or withdrawal. Conclusions Children with PRCA usually complain of anemia-related symptoms. Laboratory tests show pathogen infection in some children with PRCA, and most of children have immune disorders. Glucocorticoids have a good therapeutic effect, but some children relapse in the course of drug reduction or withdrawal. Combined treatment with prednisone and Huaiqihuang granules may have a faster onset of action and less possibility of recurrence.