G-quadruplexes (G4) are secondary four-stranded DNA helical structures consisting of guanine-rich nucleic acids, which can be formed in the promoter regions of several genes under proper conditions. Several cancer cells have been shown to emerge from genomic changes in the expression of crucial growth-regulating genes that allow cells to develop and begin to propagate in an undifferentiated state. Recent attempts have focused on producing treatments targeted at particular protein products of genes that are abnormally expressed. Many of the proteins found are hard to target and considered undruggable due to structural challenges, protein overexpression, or mutations that affect treatment resistance. The utilization of small molecules that stabilize secondary DNA structures existing in several possible oncogenes' promoters and modulate their transcription is a new strategy that avoids some of these problems. In this review, we outline the function of G-quadruplex stabilization in cancer by small-molecules with the aim to improve cancer therapy.