Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of thecountry has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted toidentify the potential risk factors for NPC development in this region. Information was collected by interviewerabout socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupationalhistory, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real timePCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay.Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001).Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III andIV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzymeactivity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke,living in poorly ventilated house and alcohol consumption were associated with NPC development among thepopulation of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphismof CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living inpoorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region ofIndia. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measuresand screening.