Direct electron transfer between resting horseradish peroxidase (HRP) and its oxidation states was observed at a gold mesh electrode in a spectroelectrochemical cell in the presence of DNA. The conversion between HRP and the oxidized species induced electrochemically was found to be reversible and parallel to that initiated chemically. DNA played an important role as electron carrier and promoted the electron transfer between HRP and the electrodes. Voltammetric results and CD spectra indicated an interaction between HRP and DNA. Moreover, the secondary structure of HRP was slightly disturbed upon mixing with DNA. The direct spectroelectrochemistry of HRP at a gold mesh electrode presented new information on its bioelectrochemical characteristics.