Objective To investigate the relationship between the protein expression of X-ray repair cross-complementing protein 3 (XRCC3) and human 8-hydroxyguanine glycosylase 1 (HOGG1) in esophageal squamous cell carcinoma (ESCC) tissue and the prognosis in ESCC patients after radiotherapy.Methods Immunohistochemical SP method was used to measure the protein expression of XRCC3 and HOGG1 in 171 ESCC tissue samples before radiotherapy.The Kaplan-Meier method was used for survival analysis,and the logrank test was used for analyzing the survival difference between negative and positive samples.The Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 87.2％ ; 140 patients were followed up for at least 1 year,136 patients for at least 2 years,and 129 patients for at least 3 years.XRCC3 was mainly expressed in the nucleus,and HOGG1 was mainly expressed in the nucleus and mitochondria,with a coincidence degree of 72.5％ (x2 =23.94,P =0.000).The patients with positive XRCC3 expression and negative XRCC3 expression had similar short-term responses (x2 =0.98,P =0.614)as well as similar survival rates,and both patient groups had a median survival time of 54 months (x2 =0.17,P =0.683).The patients with positive HOGG1 expression and negative HOGG1 expression had similar short-term responses (x2 =0.26,P =0.880) as well as similar survival rates,and both patient groups had a median survival time of 49 months (x2 =0.08,P =0.780).The multivariate prognostic analysis showed that the response evaluation and tumor length were related to the prognosis of ESCC (x2 =7.99,P =0.005 ; x2 =3.76,P =0.045).Conclusions The protein expression of XRCC3 and HOGG1 may be unrelated to the prognosis of ESCC after radiotherapy.