Abstract: OBJECTIVE To evaluate the clinical use and standardize rational drug use of methotrexate through evidenced-based medicine. METHODS A retrospective survey of 1 011 prescription for methotrexate tablets from outpatient of Hebei People's Hospital from January 2018 to June 2019 was conducted. The prescription in which methotrexate was used off-label were categorized and evaluated by Thomson grading system of Micromedex. According to the results of evaluation, the recommendations and intervention measures of off-label use were given out. RESULTS The main type of off-label use of methotrexate tablets was super indication, accounting for 90.7%, followed by super single dose, accounting for 37.4%, the highest incidence department was rheumatology. The top three clinical diagnoses were rheumatoid arthritis, Sjögren's, dermatomyositis. According to the hospital's off-label management system, analyzing evidence-based medical evidence, there were 4 types of extra-indication which 3 types were agreed to use, and one type was limited use. Six types of extra-indication and over single use at the same time were agreed to use. A type of over single was agreed to use. CONCLUSION It is a widespread phenomenon of the off-label use of methotrexate tablets. It must be strictly implement off label management system to promote safe medication.