The electrochemical properties of a modified electrode covered with 2‐[2‐(4‐nitrophenoxy)ethoxy]ethylthio‐substituted porphyrazine/single‐walled carbon nanotube hybrids were investigated. The electrochemical study revealed that the electrode mechanism is more complex in acidic conditions in comparison to neutral buffer. According to our study, the nitro groups constituting the part of porphyrazine substituents can be electrochemically reduced to the corresponding hydroxylamine moieties; surprisingly, however, the latter can be additionally transformed to o‐aminophenol/o‐iminoquinone groups, but only in acidic conditions. The electrode covered with hybrid material was used in the electrocatalytic oxidation of NADH. According to these results, it seems that after the electrochemical activation of the electrode material, 2‐[2‐(4‐nitrophenoxy)ethoxy]ethylthio‐substituted porphyrazine reveals strong electrocatalytic behavior towards NADH oxidation, owing to the appearance of reversible surface‐anchored o‐aminophenol/o‐iminoquinone intermediate redox couples. In the amperometric determination, the limit of detection (LOD) and limit of quantification (LOQ) of NADH were calculated and found to be LOD=0.16 and LOQ=0.48 μM. Moreover, the relative standard deviation of the response was 3.32 %, indicating excellent reproducibility. Thus, the novel electrode based on 2‐[2‐(4‐nitrophenoxy)ethoxy]ethylthio‐substituted porphyrazine and single‐walled carbon nanotubes present an interesting opportunity in the fields of electroanalytical and biosensing applications, and can be considered for amperometric NADH determination.