Methotrexate (MTX) is a folate analogue. Low-dose MTX is safe and well tolerated, it is now first- line therapy for the treatment of rheumatoid arthritis. Pancytopenia is an uncommon adverse drug reaction of low-dose pulse MTX therapy. This case is a 62-year-old woman with rheumatoid arthritis, congestive heart failure, chronic kidney disease. She had been treated with MTX for long- term. A few months before admission, she had increased treatment dosing, and appeared infection and pancytopenia. According to the literature review, MTX induced pancytipenia was considered dose - dependent. We discussed the pathogenesis, associated risk factor, prevent and treatment for MTX induced pancytopenia by literature review, hope to enhance drug safety.