Objective: To explore the clinical effect of etanercept in the treatment of ankylosing spondylitis and evaluate the safety of this therapy. Methods: 33 cases of patients with ankylosing spondylitis who come to our hospital for treatment were selected and divided into observation group and control group. Patients in observation group was treated with etanercept and patients in control group was treated with willow nitrogen sulfanilamide pyridine and methotrexate. The time for treating is 12 weeks. The curative effect and adverse reaction at 0, 4 , 8 and 12 weeks were evaluated respectively. The relevant observation indexes are mainly ASAS20, ASAS50, ASAS70, spinal pain, AS activity index (BASDAI), thoracic expansion degree, scoliosis, morning stiffness time, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). Results: Compared with before receiving the treatment, the level of the indexes of spinal pain, BASDAI, schober test, thoracic expansion degree, scoliosis, CRP and ESR of patients in the control group improved a lot, the difference was statistical significance (P<0.05). Similarly, these indexes in observation group had a great improvement in 8 and 12 weeks, the difference was statistically significance (P<0.05); but the level of these indexes had no statistical significance at 4 weeks (P>0.05). Compared with control group, we found out that all of the indexes been tested had a great improvement than that in the control group, the difference was statistically significant (P<0.05). The rate of adverse reaction of the observation group was 16.7%, which was obviously lower than that of the control group (55.6%), the difference between them had statistical significance (P<0.05). Conclusion: The etanercept has great clinical effect in the treatment of ankylosing spondylitis. It can improve the symptoms, signs, joint function as well as patient’s quality of life, which is safety and worth of popularizing.