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DNA or RNA G-quadruplexes are secondary structures that occur in four-stranded Guanine-rich regions formed by stacked G-tetrads. The formation of DNA or RNA G-quadruplex structures plays a key role in many cellular biological processes such as DNA replication, transcription, translation, and telomeric maintenance. As such, G-quadruplex is considered a potential target for the regulation of genes in cellular processes. Most of the abnormal gene activities cause cancer. Understanding and controlling the formation of G-quadruplex is one of the approaches for cancer treatment. Therefore, research and development of small molecules or proteins that can directly target G-quadruplex will play a key role in the development of cancer treatments and further therapeutic approaches. In this research, we will focus on analysis and discussion of the interaction between G-quadruplex and its ligands (small molecules or proteins) as well as the potentials of these ligands in cancer treatment.