Recently, it has been shown that DNA catalyzes the hydrogen evolution reaction (HER) at mercury-containing electrodes, which provide voltammetric and chronopotentiometric stripping (CPS) peaks H DNA , allowing label-free DNA determination at very low concentrations. Here, we compared DNA catalytic HER in H 2 O with catalytic deuterium evolution reaction (DER) in D 2 O. We show that in D 2 O single-stranded (ss) and double-stranded (ds) DNAs produced CPS peaks H D DNA due to DER. Compared to peaks H DNA obtained in H 2 O, peaks H D DNA were smaller and appeared at more negative potentials. Under conditions where dsDNA did not produce any peak H D DNA in D 2 O, this DNA produced in H 2 O peak H DNA . These results suggested a lack of accessible bases in the D 2 O surface-attached dsDNA. This might be attributed to the greater stability of deuterated dsDNA, better resisting the electric field effects at the negatively charged interface. The process of protonation of deuterated ssDNA was very fast in contrast to that of dsDNA, which was much slower and could be followed by CPS in a time range of tens of minutes.[a] Dr.