〔Abstract〕 Objective To explore the relationship betweenPorphyromonas gingivalis(Pg)and mitophagy in esophageal cancer cells, and to explore new therapeutic targets for esophageal cancer. Methods (1) Western blot was used to detect the phosphorylation of unc-51-like authophagy activating kinase1(ULK1) in mitochondria of the Pg infected cells and immunohistochemical method was used to detect the correlation between the expression of Pg and the phosphorylation status of ULK1 in esophageal cancer tissues.(2) Western blot, ICC and ELISA were used to detect the transfer of nucleotide blinding domain and leucine rich repeat containing family member X1(NLRX1) from cytoplasm to mitochondria, mitophagy, and the secretion levels of interleukin(IL)-6 and reactive oxygen species(ROS) under Pg infection.(3) Pg colonization in esophageal tissues of mice in each group was detected by qPCR and Pg colonization in esophageal squamous epithelial cells of mice by RNAscope. Results Compared with the untreated group, the phosphorylation level of mitochondrial ULK1(P<0.01), NLRX1 expression(P<0.001) and mitophagy(P<0.001) of esophageal cancer cells increased after Pg infection. Compared with the control group, the combined intervention group could inhibit Pg colonization in esophageal tissue and esophageal squamous epithelial cells of mice(P<0.001). Conclusion Pg promotes the translocation of NLRX1 from cytoplasm to mitochondria by up-regulating the phosphorylation level of ULK1 in the mitochondria of esophageal cancer cells, and then induces mitophagy, leading to the reduction secretion of IL-6 and ROS, and ultimately maintaining Pg colonization.