To study the efficacy and safety of combined etanercept and iguratimod in treatment of active rheumatoid arthritis. 45 patients were randomly divided into group A: etanercept+methotrexate (MTX) group; group B: etanercept+iguratimod group; and group C: iguratimod group. 45 patients with active rheumatoid arthritis treated at the hospital between July 2011 and July 2015 were divided into three groups, n = 15 in each group. Group A was treated with etanercept (subcutaneous injection at 25 mg twice weekly) in combination with MTX (initial dosage of 7.5 mg/week, and gradual increase of dosage to 15 mg/week from the fourth week). Group B was treated with etanercept (subcutaneous injection at 25 mg twice weekly) in combination with iguratimod (oral administration at 25 mg twice daily). Group C was treated with iguratimod alone (oral administration at 25 mg twice daily). Therapeutic efficacy was assessed according to the American College of Rheumatology (ACR) criteria. No statistically significant difference was not observed in the therapeutic efficacy between groups A and B, while the efficacy between groups A and C showed significant difference. After 52 weeks of treatment, ACR20 response rates were 69.12%, 63.45% and 50.24, respectively, for groups A, B and C. Group A had the response rate significantly higher than groups B and C (P<0.05). In group B, 2 patients experienced gastrointestinal discomfort. Etanercept combined with iguratimod has good safety and remarkable efficacy in treating active rheumatoid arthritis.