Abstract: Objective To observe the effect of TNF-α antagonist on quality of life of patients with ankylosing spondylitis(AS) who lacked response to traditional treatments. Methods Sixty patients with AS who met the criteria were randomly selected and observed by non-blind self-controlled trials from May 2015 to October 2016 in the Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine. All patients were treated with Yisaipu for 24 weeks and continued to follow up to 48 weeks. SF-36 scale, hospital anxiety and depression scale(HADS), Pittsburgh sleep quality index scale(PSQI) and disease activity were observed and the efficacy of ASAS20 and ASAS40 criteria were evaluated. Results After treatment for 24 weeks, 50 patients(83.3%) have met ASAS20 efficacy criteria and 36 patients(60.0%) achieved ASAS40 efficacy criteria. Some patients still maintained a stable efficacy after the reduction of Yisaipu during the following 24 weeks. While the disease activity and pain of patients were fully improved, the SF-36 scale(except MH) and PSQI scores were significantly improved(all P<0.01), especially BP and sf36-pcs improved the most obviously. Although the scores of HA and HD of patients before treatment were higher than those of healthy controls, there was no significant improvement at 24 and 48 weeks after treatment(all P>0.05). The disease activity indicators such as ASDAS-CRP and BASDAI indexes were negatively correlated with some dimensions of SF-36, but not with HA, HD, MH. Conclusion Yisaipu is effective and safe in treating AS patients who lack response to traditional therapy. It can significantly improve their quality of life and sleep, but has no effect on HADS and MH.