In this work we studied how backbone chemical modifications, such as 2'-O-methyl, phosphorothioate, L-form nucleotides and locked nucleic acid, on G-quadruplex based DNAzymes would affect their peroxidase activity. Our results indicate that 2'-O-methyl modification facilitates the formation of a perfectly compacted parallel structure and significantly promotes peroxidase activity of G-quadruplex based DNAzymes.