The WT1 gene is an important oncogene, and its overexpression is considered as an effective target for anticancer therapy. Regulation of its gene transcription is one way for WT1 -targeting drug design. Recently, in silico analysis of some oncogene promoters like WT1 showed some guanine-rich regions with the ability to form G-quadruplex structures. Ligands like 5,10,15,20-tetra( N -methyl-4-pyridyl)-porphine (TMPyP4) have predominant effect on G-quadruplex stabilization. The aim of this study was to understand the effect of TMPyP4 on WT1 gene transcription via stabilization of promoter G-quadruplexes. We examined the formation of new G-quadruplex motifs in WT1 promoter in the presence of TMPyP4. In order to understand the nature of its interaction with WT 1 promoter quadruplexes, differential pulse voltammetry (DPV), circular dichroism (CD), polyacrylamide gel electrophoresis, electrophoretic mobility shift assay (EMSA), polymerase chain reaction (PCR) stop assays, and quantitative RT-PCR were performed. According to the results, the WT 1 promoter can form stable intramolecular parallel G-quadruplexes. In addition, after 48 and 96 h of incubation, 100 μM TMPyP4 reduced the WT1 transcription to 9 and 0.4 %, respectively, compare to control. We report that ligand-mediated stabilization of G-quadruplexes within the WT 1 promoter can silence WT1 expression. This study might offer the basis for the reasonable design and improvement of new porphyrin derivatives as effective anti-leukemia agents for cancer therapy.