Abstract: G-quadruplexes (G4s) is a secondary structure of nucleic acid formed by the folding of DNA or RNA rich in tandem repeat guanine (G). It widely exists in the genomes of all organisms and participates in the regulation of gene replication, transcription and translation. G4s has aroused interest from researchers because of its key biological functions. In the early days, researchers mainly focused on the study of G4s in cancer and used it as the target of antineoplastic drugs. Recently, research on viral genomics has found that many G4s appear in the regulatory regions of the viral genome and play a key role in regulating the life cycle of the virus. With the emergence of new viruses in the human population and the rapid mutation of existing viruses, it is necessary to develop new antiviral targets and drugs. Most of the existing antiviral drugs aim mainly at viral proteins, with few studies on direct nucleic acid targeting. This paper summarizes the application of small molecular ligands targeting G4s against virus in order to provide some reference for the research and development of antiviral drugs based on G4s.