Methotrexate (MTX) is an effective medication in the treatment of rheumatoid arthritis (RA), other rheumatic diseases and various solid tumors. However, its side effects, including gastrointestinal discomfort, oral ulcers, and especially bone marrow suppression, could be fatal and require special attention, particularly in patients with renal failure. We present two hemodialysis patients with RA who presented with a complication of severe pancytopenia after treatment with MTX. After receiving various supportive and blood purification treatments, both patients recovered. We reviewed twenty-four pancytopenia patients on dialysis associated with methotrexate. Among these patients, high morbidity and mortality were observed, indicating that MTX should be used cautiously in the absence of alternatives in such a population. Compared with the patients who recovered, the deceased patients showed a lower level of leukocytes. Which dialysis method might be the best choice is unclear. The mode of renal replacement therapy can be chosen according to the actual situation.