OBJECTIVE: To study the effects of etanercept combined with cyclophosphamide on related indexes of patients with rheumatoid arthritis complicated with interstitial pneumonia (RA-IP). METHODS: A total of 84 RA-IP patients were randomly divided into control group (42 cases) and observation group (42 cases). Control group was given Etanercept for injection 25 mg subcutaneously twice a day. Observation group was additionally given Cyclophosphamide tablets 50 mg orally, once a day, increasing by 50 mg every 7 d later, with maximum dose lower than 100 mg, for consecutive 2 weeks, 2 weeks later repeated, on the basis of control group. Both groups were treated for 3 months. The number of joint tenderness and joint swelling, morning stiffness time, VAS score, DAS28 score, CRP, ESR, serum rheumatoid factor (RF), TNF-α, p(O2), VC, clinical score, imaging score, physiological score and the occurrence of ADR were observed in 2 groups before and after treatment. RESULTS: After treatment, the number of joint tenderness and joint swelling, morning stiffness time, VAS score, DAS28 score, the levels of CRP, ESR, RF and TNF-α, clinical score, imaging score, physiological score in 2 groups were significantly lower than before treatment; the observation group was significantly lower than control group. p(O2) and VC of 2 groups were significantly higher than before treatment, and the observation group was significantly higher than the control group, with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS: Etanercept combined with cyclophophamide in the treatment of RA-IP can improve clinical symptom, signs, life quality and lung function without increasing the occurrence of ADR.