Trichosporon asahii (T. asahii) is an uncommon fungal pathogen rarely seen in patients with hematologicmalignancies. Although appropriate therapy is started, infection with T. asahii usually leads to mortality. Here, we describe two patients developed severe T. asahii infection and secondary HLH. Despite rapid identification of T. asahii and negative blood cultures achieved by prompt initiation of treatment with voriconazole, fever and pancytopenia, persisted and both developed hepatosplenomegaly, and their clinical state worsened. Bone marrow aspiraton revealed hemophagocytosis. Elevated ferritin, triglyceride levels were seen. The first patient did not receive HLH directed therapy and died with multiple organ dysfunctions. Prompt diagnosis and treatment of secondary HLH led to rapid improvement in clinical and laboratory abnormalities in the second patient and kept her alive. We suggest that HLH may present as a secondary condition, accompanying a severe infection with T. asahii may, at least in part, contribute to high mortality rates in these cases.