Aim To explore the potential role of activated X-box-binding protein-1(XBP-1)in apoptosis of endothelial cells induced by high mobility group box-1 protein(HMGB1）. Methods The HUVEC12 were divided into three groups: control group, HMGB1 stimulating group, virus interference and HMGB1 stimulating group(XBP1 was silenced and then HMGB1 was added）. The spliced XBP1(sXBP1)gene expression was measured by RT-PCR, Caspase-3 protein expression was measured by Western blot, and the apoptosis was analyzed by fluorescence staining with Annexin-V and PI staining. Results Compared with control group, sXBP1 gene expression was up-regulated, Caspase-3 protein expression was up-regulated, cell apoptosis rate was increased(all P<0.05)in HMGB1 stimulating group. While compared with control group, sXBP1 gene expression change was not significant, Caspase-3 protein expression variation was not significant, and the cell apoptosis rate was not increased in virus interference and HMGB1 stimulating group(all P>0.05）. Compared with HMGB1 stimulating group, sXBP1 gene expression and Caspase-3 protein expression was down-regulated(P<0.05）, and cell apoptosis rate was decreased(P<0.05)in virus interference and HMGB1 stimulating group. Conclusion The XBP1 played an important role in endothelial cell apoptosis induced by high mobility group box-1 protein.