Objective To observe the therapeutic effect of tumor necrosis factor inhibitor (Etanercept) on intractable ankylosing spondylitis (AS) related hip joint lesion. Methods Thirty-five patients with AS with unilateral or bilateral hip joints pain and limitation of joint motion were included into this study. The patients' conditions were not controlled under standard treatment by non-steroidal anti-inflamma-tory drug and antirheumatic medications. The clinical trial was designed as a prospectiveopen study, 35 pati-ents received Etanercept 50 mg once a week for 12 weeks, combined with methotrexate (MTX) 10 mg once a week. Parameters including Harris hip score, Bath ankylosing spondylitis radiologic index-hip (BASRI-hip), Bath ankyiosing spondylitis disc.use activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were evaluated and side effects were observed before and after the treatment. Results Fifty-five hip joints were involved in 35 patients, in which unilateral hip involvement in 15 patients and bilateral in 20 patients. Harris score of the hips iner-eased significantly from 51±4 before treatment to 86±5 (P=0.000) after treatment ; Before and after treatment, BASDAI changed from 6.4±1.2 to 4.4±0.8 (P=0.000), BASFI was changed from 6.3±1.1 to 3.4±0.8 (P=0.000), before and after treatment ESR was changed from (68±28) mm/l h to (25±6) mm/l h (P=0.001), CRP changed from (59.1±22.3) mg/l, to (6.9±1.1) mg/L (P=0.000) before and after treatment respectively, but BASRI-hip was not changed obviously before and after treatment. No tuberculosis and serious side effects was observed during the treatment and follow-up period. Conclusion Etanercept, when combined with methotrexate, could be used to treatintractahle AS-related hip joint lesions. This regimen could improve the hip joint function and control the disease activity without serious side effects.