Objective. High mobility group box 1 (HMGB1) is a late inflammatory factor participating in the pathogenesis of various autoimmune and inflammatory diseases. In the current study, we analyzed the association between serum levels of HMGBI and clinical features of AS patients before and during treatment. Methods. Serum HMGB1 was detected in 147 AS patients and 61 healthy controls using 1/LISA. We evaluated the association between HMG B1 and extra-articular manifestations as well as disease severity indices. Among these AS patients, 41 patients received close follow-up at 1, 3, and 6 months after treatment This group comprised 25 patients treated with anti-TNF-alpha biologics and 16 patients receiving oral NSAIDs plus sulfasalazine. Results. The serum HMGB1 of AS patients was significantly higher than in healthy controls and positively correlated with BASDAI, BASFI, ASDAS-ESR, ASDAS-CRP, ESR, and CRP, but not with HLA-B27, anterior uveitis, and recurrent diarrhea. There was no significant difference between patients with radiographic damage of hip joints and those without. We observed that serum HMGB1 paralleled disease activity after treatment. Conclusion. Serum level of HMGB1 is higher in AS patients, and to some extent, HMG B1 can reflect the activity of AS and be used as a laboratory indicator to reflect the therapeutic response.