Objective To investigate the difference between acupoint injection and subcutaneous injection of etanercept in the treatment of ankylosing spondylitis(AS). Methods Sixty patients with AS were divided into experimental group and control group by random number table method, 30 cases in each one. On the basis of oral diclofenac sodium enteric-coated tablets, patients in the experimental group were injected with etanercept at ashi point of bilateral sacroiliac joint,while patients in the control group were injected with etanercept at bilateral lateral deltoid muscle of the upper arm subcutaneously for a course of 12 weeks. Efficacy was evaluated at 2 weeks, 4 weeks, 8 weeks and 12 weeks. Results After one course of intervention, CRP, ESR, VAS score, bath ankylosing spondylitis disease activity index(BASDAI), bath ankylosing spondylitis functional index(BASFI), and morning stiffness time of patients in each group all decreased, and the differences were statistically significant(P<0.05)； 2 weeks treatment group on the BASFI score improvement is better than that of control group(P<0.05); 4 weeks treatment of the experimental group on the VAS score, morning stiffness time, BASFI improved better than that of control group (P<0.05); The improvement of VAS score, morning stiffness time, BASDAI, BASFI and CRP in the 8-week treatment group was better than that in the control group(P<0.05). The improvement of VAS score, morning stiffness time, BASDAI, BASFI and CRP in the 12-week treatment group was better than that in the control group (P<0.05). Conclusion Etanercept is effective in the treatment of AS, and injection of etanercept at point a is better than subcutaneous injection in improving patients' VAS score, morning stiffness time, BASDAI, BASFI and CRP.