Provided is an inhibitor of HMGB protein-mediated immune response activation, comprising one or more compounds selected from the group consisting of phosphorothioate oligonucleotides and derivatives thereof. Also provided is a method for screening an inhibitor or promoter of HMGB protein-mediated immune response activation, comprising: a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance； a assaying step of assaying the HMGB protein bound to the labeled nucleic acid； and a determination step of determining that the test substance is an inhibitor of HMGB protein-mediated immune response activation in the case that the quantity of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than the quantity of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance, and determining that the test substance is a promoter of HMGB protein-mediated immune response activation in the case that the quantity of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is greater than the quantity of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.
