It has recently been shown that HSV-1 infection induces widespread defect in host gene transcription termination while viral genes are unaffected. However, The underlying mechanism remain poorly understood. According to our sequencing data, ICP27 as an immediate early protein of HSV-1 was involved in disrupting host transcription termination. To elucidate the underlying mechanism, we performed IP-MS to figure out interaction proteins with ICP27. Other than export proteins, 3’ end processing factors strongly associated with ICP27 based on this IP-MS data. Pre-mRNA 3’ end processing is required for transcription termination. As expected, this MS data as well as our in vitro and in vivo data suggested that ICP27 functions in pre-mRNA 3’ end processing to regulate transcription termination in a sequence dependent manner.