ObjectiveTo explore new mechanisms of cross-species regulation of plant microRNA (miRNA) to regulate human health and disease.MethodThe recently relevant literatures on the new mechanisms of cross-species regulation of the plant miRNA for the health and disease of human were reviewed.ResultsThe phytochemicals played an important role in the maintaining human health and regulating diseases, and the plant miRNA cross-species regulation also played an important role in it. Its possible regulatory mechanism was that the mature plant miRNA came into the animal body through the gastrointestinal tract. It firstly passed through the gastrointestinal tract and then came into the microvesicles secreted by the small intestine. It was targeted to the organ or tissue through passing of the animal circulatory system. The plant miRNA passing through the gastrointestinal tract was highly matched with the target mRNA to perform its biological regulatory role.ConclusionsAlthough studies have confirmed that plant miRNA can regulate animal specific biological functions across gastrointestinal tract and it provides an experimental basis for plants to participate in new mechanisms for regulating occurrence and development of human health and disease, whether or not miRNA in food is affected by way it is processed, transported, stored, and extent to which it is affected, remains to be explored. At the same time, content of plant miRNA in animals is very low and types of plant miRNA in different animals are not same. Although the above issues have been unresolved, it is believed that with research progresses, mastering mechanism of miRNA cross-species regulation will greatly help to prevent human diseases and maintain health of body.