Abstract: The invention provides a method for treating cerebral apoplexy and hyperbilirubinemia by the compound or reagent for competitively inhibiting or blocking combination of bilirubin and the TRPM2 channel. The compound or the reagent is competitively combined with the D1069 residue of TRPM2 channel (the analogous D1066 residue of the mouse TRPM2). It is verified that bilirubin can serve as an extracellular endogenous agonist to be directly combined with the TRPM2 channel to aggravate brain tissue damage caused by stroke and hyperbilirubinemia, K928 and/or D1069 residues are key amino acid residues for playing roles. When the K928 and/or D1069 residues are mutated or competitively combined, the bilirubin is prevented from activating the TRPM2 channel; wherein D1069 residue mutation can effectively antagonize the nerve injury effect caused by bilirubin, which would be a therapeutic target for relieving and treating ischemic stroke and hyperbilirubinemia related brain damage.