The main purposes of this study were to identify the major determinants of nasopharyngeal carcinoma (NPC) in the high-background radiation areas (HBRA) in Yangjiang, China and to evaluate their potential confounding effects on the NPC risk associated with exposure to high background radiation. A matched case-control study was conducted using those who died of NPC during the period 1987-1995. Two controls were randomly selected for each case from those who died from causes other than malignancies and external causes. Cases and their controls were matched with respect to sex and the years of birth and death (+/- 5 years). Study subjects' next-of-kin were interviewed using a standardized questionnaire to collect information on socioeconomic status, dietary habits, tobacco smoking and alcohol consumption, disease history, pesticide use, medical X-ray exposure, the family history of NPC and so on. We succeeded in interviewing 97 cases and 192 controls. Univariate conditional logistic regression analysis showed that NPC risk was associated with the consumption of salted fish, homemade pickles, and fermented soy beans, education levels, the history of chronic rhinitis, and the family history of NPC. Multivariate conditional logistic regression analysis revealed that education levels (Odds ratio (OR) for middle school or higher levels vs. no school education = 3.8, 95% CI = 1.2 to 11.8), salted fish intake (OR = 3.2, 95% CI = 1.7 to 6.1), the history of chronic rhinitis (OR = 3.6, 95% CI = 1.3 to 10.1), and the family history of NPC (OR = 14.2, 95% CI = 2.7 to 73.4) were independent risk factors of NPC. Tobacco smoking (OR = 1.2, 95% CI = 0.7 to 2.1), and alcohol consumption (OR = 0.9, 95% CI = 0.5 to 1.9) were not significantly related to NPC risk. The ORs of NPC risk comparing HBRA and a nearby control area before and after adjustment for the major risk determinants identified in the present study were 0.86 (95% CI = 0.50 to 1.50) and 0.87 (95% CI = 0.45 to 1.67), respectively. Salted fish intake was a strong risk factor of NPC. Education, the history of chronic rhinitis and the family history of NPC were also related to NPC risk. The exposure to high background radiation in HBRA of Yangjiang was not related to NPC risk with or without the adjustment for those major risk determinants of NPC.