Abstract: Histamine H₄ receptor (H₄R), one of the subtypes of histamine receptors, is mainly expressed in the immune system and gastrointestinal tissues. The binding of histamine, the endogenous ligand of H₄R, to H₄R can lead to a significant increase of proinflammatory factors such as interleukin, and recruit immune cells to the inflammatory site, promoting the occurrence and development of a variety of inflammations and cancers. H₄R can be used as a potential drug target for the treatment of inflammatory bowel disease, allergic rhinitis, atopic rhinitis, allergic asthma, rheumatoid arthritis, neuropathic inflammation, cancer and other diseases. Therefore, the study of novel selective H₄R antagonists is of great significance for its drug development. This paper reviews the research progress of H₄R and its antagonists in the hope of providing some reference for the research in this field.