The aim of this study was to investigate the effectiveness and safety in the treatment of thrombocytopenia in hemophagocytic lymphohistiocytosis (HLH) by recombinant human thrombopoietin (rhTPO). A prospective randomized study was conducted between March 2010 and December 2011 in 40 patients with adult HLH whose blood platelet counts (BPC) were lower than 40 x 10(9)/L. The 40 patients were randomly assigned into the rhTPO group or control group based on sex, age, primary disease, and BPC (20 in each group). All patients were given conventional systemic therapy for HLH. The rhTPO group was administered by subcutaneous injection of rhTPO at a dose of 300 IU/kg Qd. The BPC, platelet transfusion, bleeding, and survival rate in the two groups were monitored and compared. There was no significant difference in BPC between the two groups before the treatment. Two weeks after the treatment, the BPC of the rhTPO group was significantly higher than that of the control group at every time point (P < 0.05). Although there was no significant difference in skin and mucous membrane bleeding between the rhTPO group and control group, however, the number of patients presented with gastrointestinal bleeding, urinary tract bleeding, and pulmonary bleeding in the control group were higher than that in the rhTPO group (P = 0.013). The frequency of platelet transfusion in the control group (7.25 per patient, 145 in 19 patients) was significantly higher than that in the rhTPO group (2.25 per patient, 45 in 14 patients) (P < 0.01). There was no significant difference in the survival rate between the two groups. The average recovery time of platelets to normal levels in the rhTPO groups was shorter than that in the control group (the rhTPO group vs the control group: 13.43 +/- 4.62 D vs 18.00 +/- 3.98 D, P = 0.013). In the early stage of HLH treatment, rhTPO combined with conventional systemic therapy can restore the BPC to normal level within a shorter period of time, reduce the frequency of platelet transfusion and severe bleeding.