Abstract: Innovating the action targets and mechanism of pesticides represents one of the critical scientific challenges necessitating resolution within the realm of pesticide science research. 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an essential enzyme in the tyrosine metabolism pathway, with varying metabolic roles across different organisms. Exploratory research indicates that HPPD plays a substantial role in pharmaceuticals and herbicide applications. Recent studies unveiled the potential HPPD inhibitors in antifungal agents and mosquito repellents, emphasizing its versatile and promising applications. Consequently, this review summarizes HPPD's physiological roles in diverse organisms, detailing its metabolic functions in humans, blood-feeding arthropods, plants, and fungi. It provides a comparative analysis of HPPD crystal structures from different species and discusses its applications in medicine and pesticides (herbicides, insecticides, and fungicides) along with future research perspective.