Massive necrosis is the dominant feature of APAP –induced ALI [2-6] and necrotic tissue passively releases HMGB1 [7-9], an important late inflammatory mediator that was well studied in sepsis [10], and HMGB1 contributes to liver injury [11,12]; this indicates that HMGB1 might play an important role in the pathogenesis of APAP hepatotoxicity. The gene discussed is HMGB1; the disease is Sepsis.