〔Abstract〕 To investigate the regulatory role of Porphyromonas gingivalis (Pg) infection on the EGFR/ GSK3 βsignaling axis , and its impact on epithelial-mesenchymal transition (EMT) and cetuximab (Ctx) resistance in esophageal squamous cell carcinoma (ESCC) . Methods Single cell RNA sequencing was employed to perform differential analysis of cellular subpopulations , identifying differentially expressed genes in ESCC tissues infected and non-infected with Pg. IHC was conducted to assess the expression of Pg and epidermal growth factor receptor ( EGFR) in ESCC tissues . Western blot , RT-PCR , and IF staining were performed to evaluate EGFR expression in Pg infected ESCC cell lines KYSE70 and TE1 . ESCC cells were treated with Pg and EGFR inhibitor Ctx , and di- vided into four groups : control (NC) group , Pg group , Ctx group , Pg + Ctx group . Cell proliferation , migration and invasion abilities were evaluated using CCK-8 , plate cloning , wound healing and Transwell assay . Western blot analysis was performed to detect the expression of EMT and EGFR/GSK3 βsignaling pathway-associated proteins and their phosphorylation levels . Transforming growth factor-β1 ( TGF-β1) was used to induce EMT in ESCC cells , promoting a transition from the epithelial phenotype to mesenchymal-like phenotype . The differential effects of Ctx on these two phenotypic states were subsequently compared . Results Epithelial cells were predominantly enriched in Pg-positive tissues , and Pg infection promoted the upregulation of EGFR expression in ESCC cells . Compared to the NC group , Pg treatment significantly enhanced the proliferation , invasion and migration capabili- ties of ESCC cells , and also increased chemoresistance to Ctx and reduced its antitumor efficacy . Pg induced EMT in ESCC cells via the EGFR/GSK3 βsignaling pathway . Notably , Ctx exhibited markedly weaker inhibitory effects on mesenchymal-like cells compared to epithelial ESCC cells . Conclusion Pg promotes ESCC cells prolif- eration , invasion and migration by regulating EMT through the EGFR/GSK3 βsignaling pathway , and enhances chemoresistance to Ctx .