【Objective】To explore the interactions between DNA-repair genes and EBV in nasopharyngeal carcinoma. 【Method】 A matched case and control design (case/control=755/755) was constructed for the population who were mainly speaking Cantonese in Guangdong Province. Clinical epidemiological data were collected

and their peripheral blood samples were subjected to EBV antibody test and SNP genotyping. Analysis of interactions between DNA-repair genes (168 tagging SNPs located in 104 genes involved in DNA repair pathways) and EBV was implemented by using the ensemble decision forest method. 【Results】 The interactions between MDC1

ATM

GTF2H4

MLH1

RAD51L1

XPC

GTF2H1

and EBV were statistically significant after Bonferroni adjustment

with P values of 7.62×10-5

8.20×10-5

8.55×10-5

1.60×10-5

1.80×10-4

2.20×10-4

and 2.42×10-4

respectively. Their OR (95%CI) values were 15.97 (4.17-61.11)

11.32 (7.22-25.45)

15.94 (4.17-64.01)

5.38 (4.88-6.74)

151.47 (53.79-380.39)

40.92 (15.09-112.67) and 142.38 (53.38-377.5)

respectively. Further bioinformatics gene network analysis revealed that these genes might modify predisposition to nasopharyngeal carcinoma in the Guangdong population via imposing an impact on the DNA replication of EBV or in other ways that are direct or indirect. 【Conclusion】The interactions between DNA repair genes and EBV might be another important mechanism for the susceptibility to nasopharyngeal carcinoma.