We newly developed a histamine-triggered electrochemical switching aptazyme by utilizing a hemin molecule and a hemin-targeting aptamer (AptDNA) complex (hemin/AptDNA). We spectroscopically and electrochemically found that the electroactivity of hemin/AptDNA is suppressed or restored in the presence or absence of histamine, respectively. The observed hyperchromicity of the Soret band of hemin at 404 nm showed the interaction of hemin with the G-quadruplex structure of AptDNA. The absorbance at 418 nm for the hemin/AptDNA solution increased in the presence of dihydrogen peroxide (H2O2) and 2,2’-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid (ABTS), where the colorless ABTS2– was oxidized to the green ABTS•–. These results led us to conclude that hemin/AptDNA worked as a redox aptazyme for the redox reaction of H2O2 and ABTS. The presence of histamine inhibited this reaction. This was also electrochemically ascertained. Electrochemical investigation demonstrated that the reduction reaction of H2O2 was facilitated by hemin/AptDNA compared with the case of AptDNA and that the reaction was restrained by the addition of histamine to the solution. These spectroscopic and electrochemical investigations revealed that the electroactivity of hemin/AptDNA is switched on/off in the presence/absence of histamine as a redox aptazyme, respectively.