We conducted a quantitative proteomic analysis of HGFs from early to late HSV-1 infection stage using DIA-based liquid chromatography-tandem mass spectrometry (LC-MS/MS). This work aimed to identify host factors variations and provide information on the various cellular and molecular pathways activated in HGFs. These results help to understand pathological process post HSV-1 infection in periodontal tissues and their potential role in pathogenic mechanisms.