Aim:To investigate the effect of Fusobacterium nucleatum(Fn)on the expressions of ferroptosis related protein hypoxia-inducible factor-1α(HIF-1α)and glutathione peroxidase 4(GPX4)in esophageal squamous cell carcinoma(ESCC)and prognosis of ESCC patients.Methods:ESCC KYSE30 and KYSE150 cells were allocated into 4 groups:control group,Fn infection group for 12 hours group,Fn infection group for 24 hours group and Fn infection group for 48 hours group.ROS and MDA kits were used to detect the content of oxidative stress indexes in cells.IC50 of cisplatin(CDDP)on KYSE30 and KYSE150 cells was detected by CCK8 kit,and the expression levels of HIF-1α and GPX4 were detected by Western blot.Fn infection in 222 cases of ESCC and adjacent normal esophageal tissues were detected by RNAscope tech-nique,and the expression of HIF-1α and GPX4 was detected by immunohistochemistry.Kaplan-Meier method was used to draw survival curves of ESCC patients with positive or negative Fn infection.Results:Fn infection induced the high expres-sions of HIF-1α and GPX4 protein in KYSE30 and KYSE150 cells,enhanced the level of oxidative stress,and decreased the response to CDDP in a time-dependent manner(P<0.05).The positive rates of Fn infection,HIF-1α and GPX4 protein ex-pression in ESCC tissue were higher than those in adjacent normal esophageal tissue(P<0.05).In ESCC patients,the posi-tive rate of Fn infection was increased in males,and patients with smoking history,drinking history,low tumor differentia-tion,tumor invasion depth in fibrous membrane,lymph node metastasis,TNM stage Ⅲ/Ⅳ(P<0.05).The survival of ESCC patients with Fn infection was worse than that without Fn infection after operation(P<0.001).Conclusions:Fn infection can induce ferroptosis of ESCC,which may be associated with poor prognosis of ESCC patients.