Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Genetic susceptibility is a major contributing factor in determining the individual risk of NPC in these areas. To test the association between NPC and variants in regenerating gene 1A (REG1A), we conducted a hospital-based case-control study in a Cantonese-speaking population from Guangdong province.We endeavored to determine whether genetic variants of the REG1A gene were associated with the risk of NPC amidst the Cantonese population in a hospital-based case-control study using polymerase chain reaction-restriction and direct sequencing analysis in 211 NPC patients and 150 healthy controls. The association between NPC risk and the 14C/T, 20C/T, 369G/T, 1201A/G, and 2922C/T polymorphisms was examined after adjustment for age and sex.We found an increased risk of developing NPC in individuals with REG1A 2922C/T variant genotype (p = 0.003, OR 0.419, 95% CI 0.235-0.746), and after adjustment for sex and age (p = 0.003, OR 0.406, 95% CI 0.226-0.732). No association between other polymorphisms (14C/T, 20C/T, 369G/T, and 1201A/G) and the risk of NPC was observed, before or after adjustment for age and sex.Our findings suggest that the REG1A 2922C/T polymorphism is associated with an increased risk of developing NPC in a Cantonese population from Guangdong province. Larger studies are required to confirm our findings and unravel the underlying mechanisms.