Objective To retrospectively analyze the diagnosis and treatment of multicentric Castleman's disease (MCD) ,and review related literatures. Methods A total of six patients were first-ever diagnosed as MCD and treated with combination chemotherapy and/or interferon α. The clinical manifestation, laboratory findings and therapeutic strategies were recorded in detail. Results In the six HIV-negative patients, histologically, four of them were diagnosed with plasma cell type of Castleman's disease, two with mixed type. All the six patients showed multiple lymphadenopathy, polyclonal hypergammaglobulinemia and hypoalbuminemia. One of the two patients treated with interferon α achieved complete remission, and the other,who showed no effects with hormone and combination chemotherapy ,achieved sustained partial remission after treatment with interferon α for 3 months. Of the four patients treated with combination chemotherapy, three achieved partial remission, and one died of no effects. Conclusions Interferon α and combination chemotherapy might be the most effective and convenient therapeutic methods for MCD. Serum albumin level may be used as a diagnostic and monitoring index for MCD.