High mobility group box 1 (HMGB-1) has recently received attention as a late mediator of lipopolysaccharide-induced shock, and is thought to function as a mediator in such a disorder as multi-organ failure (MOF). In Japan, we have access to an immobilized polymyxin B fiber column using a direct hemoperfusion (PMX-DHP) for patients with septic shock to improve hemodynamics and organ dysfunction. In this study, we looked at HMGB-1 levels in each category based on the sequential organ failure assessment (SOFA) scores to further dissect its importance in specific aspects of organ failure in patients undergoing PMX-DHP. Sixty patients with septic shock (40 survivors and 20 non-survivors). We analyzed HMGB-1 and IL-6 levels before and after PMX-DHP and defined organ failure as two or more SOFA points. There was a significant positive correlation between SOFA score and HMGB-1 level (P<0.05). The HMGB-1 level before PMX-DHP significantly increased as the number of organ failures increased (P<0.01: comparing 2 versus 5 organ failures). IL-6 levels decreased after PMX-DHP (P<0.05 compared with before PMX-DHP), but HMGB-1 levels remained unchanged. HMGB-1 levels of survivors with organ failure in liver decreased after PMX-DHP, but those of non-survivors significantly increased 24h after PMX-DHP compared with before PMX-DHP (P<0.01). In non-survivors with organ failure in liver, HMGB-1 levels were significantly higher than among survivors 24h after PMX-DHP (P<0.01). Our results indicate that HMGB-1 is a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP.