The side effects of methotrexate are gastrointestinal irritation, liver damage, kidney impairment, lung lesions, bone marrow suppression, allergic reactions, and infections. The side effects of leflunomide are mainly diarrhea, itching, reversible elevation of liver enzymes (ALT and AST), alopecia, and rash. 1.Methotrexate adverse reactions: (1) Gastrointestinal reactions: including stomatitis, mouth and lip ulcers, pharyngitis, nausea, vomiting, abdominal pain, diarrhea, gastrointestinal bleeding. Loss of appetite is common; (2) Hepatic impairment: including jaundice, increased alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, etc. Prolonged oral intake may lead to hepatocellular necrosis or even hepatic steatosis; (3) Renal damage: when applied in large doses, hematuria, proteinuria, oliguria, azotemia or even uremia may occur; (4) Lung lesions: pneumonia or pulmonary fibrosis; (5) Bone marrow suppression: mainly leukopenia and thrombocytopenia, anemia and platelet drop with skin or visceral bleeding; (6) Allergic reactions: alopecia, skin redness, itching or rash; (7) Infection: can be complicated by low white blood cells. 2. leflunomide adverse reactions: Weakness, abdominal pain, back pain, hypertension, anorexia, diarrhea, dyspepsia, gastroenteritis, elevated liver enzymes, nausea, mouth ulcers, vomiting, weight loss, joint dysfunction, tenosynovitis, dizziness, headache, bronchitis, cough, respiratory tract infections, pharyngitis, alopecia, itching, rashes, and urinary tract infections. It is recommended to take methotrexate and leflunomide under the guidance of a doctor and avoid self-medication.