Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP/HUS) is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal function abnormalities, and fever. Coexistence of TTP/HUS and adult onset Still's disease (ASD) is extremely rare. We report the case of a 46-year-old woman who presented with fever, arthritis, myalgias, petechia on skin and confusion five years after the onset of ASD. Thrombocytopenia, renal failure, marked elevation lactate dehydrogenase, and red cell fragmentation on peripheral blood smear were observed. We made a diagnosis of TTP/HUS associated with ASD, according to physical examination and characteristic laboratory data. She recovered from the TTP/HUS following daily sessions of therapeutic plasma exchange with fresh frozen plasma replacement and glucocorticoid therapy. Awareness of the possible development of TTP/HUS in ASD is important for early diagnosis and treatment.