Background and purpose: Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating hormone receptor) confers an increased risk of benign thyroid disorders. Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer (NMTC). To explore the hypothesis that polymorphic variation in these genes affects the risk of NMTC. Methods: Tg A7589G and TSHR C253A polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (FCR-RFLP) method, to analyze the relationship between the Tg and TSHR gene polymorphisms and NMTC in NMTC and control groups. Results: Among 360 cases, there was no statistic difference in the frequencies of genotype and allele of TSHR C253A between NMTC and control groups. There were Tg A7589G polymorphisms in the 360 cases. The frequencies ofAG+GG genotype in NMTC group were significantly higher than those in control groups (P<0.05). The frequencies of G allele in NMTC group were significantly higher than those in control groups (P<0.001). Conclusion: There were Tg A7589G gene polymorphisms in NMTC and control groups. G allele may be the predisposing gene of NMTC.