DNA sequences with repetitive G-rich structural motifs, which form special structures called G-quadruplexes, widely exist in the human genome. Here we report the general peroxidase activity of G-quadruplex-hemin complexes and discuss the connection between peroxidase activity and G-quadruplex structures. The high peroxidase activity of hemin complexed with intramolecular parallel G-quadruplex-forming sequences in gene promoters (such as c-Myc, VEGF, c-Kit21, HIF-1alpha, and RET) may imply a potential mechanism of hemin-mediated cellular injury. This peroxidase activity has also been demonstrated to be applicable for screening G-quadruplex ligands (potential anticancer reagents) using colorimetric and visual detection strategies.