Herpes simplex virus type 1 (HSV-1) DNA polymerase accessory subunit UL42 is a multifunctional protein encoded by the viral UL42 gene. It is one of the components of HSV-1 DNA polymerase. HSV-1 UL42 plays an important role in regulating virus replication and in suppressing the host's innate immune response. UL42 is capable of improving the processivity of DNA polymerase catalytic subunit UL30, and functions as a binding mediator between UL30 and DNA template chain, introducing DNA polymerase into nuclear and improving the fidelity of virus replication. In addition, UL42 also contains a peptide which can inhibit the activity of DNA polymerase, suggesting a negative regulatory effect during viral replication. Recent studies indicate that UL42 can block the TNF-α-mediated NF-κB signaling pathway and the function of IRF-3, implying that its ability in evading host’s innate immune response, but the specific mechanism is unclear. A description of research progresses on the structure, functions, mechanism and antiviral drug developments of HSV-1 UL42 could lay a foundation to further researches.