Abstract: Herpesviruses(HV) are a group of highly infectious pathogens with double-stranded DNA structures that cause a variety of human clinical diseases, including varicella-zoster, herpes simplex, EBV-associated lymphoproliferative disorders, and cytomegalovirus infections. The helicase-primase(HP) complex plays an essential role in the DNA replication process of HV, making it a critical target for antiviral therapy. In recent years, significant progress has been made in the study of inhibitors of this complex. By reviewing the HV life cycle, the DNA replication process and the function of the HP complex, as well as presenting the research progress of the helicaseprimase complex inhibitor(HPI), which includes the structural optimization process of some of them, and discusses the future research focuses of HPI, we provide a reference for the anti-herpesvirus drug development.