In the light of the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and thyroid cancer (TC) exist objection, a meta-analysis of the MTHFR C677T polymorphism with thyroid cancer risk was performed. All the available studies were identified through a search of the PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database (CBM) up to March 2014. The association between the MTHFR C677T polymorphism and thyroid cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of five independent studies with 2,554 cases and 2,671 controls were included in our meta-analysis. Significant association was found between MTHFR C677T polymorphism and thyroid cancer risk in recessive model in overall populations (TT vs.
Tc/cc: OR = 1.88, 95 % CI = 1.59-2.21, P = 0.00), but there was no association between MTHFR C677T polymorphism and thyroid cancer risk found in other four models in overall populations (T vs. C: OR = 1.25, 95 % CI = 0.96-1.62, P = 0.10; TT vs. CC: OR = 1.11, 95 % CI = 0.93-1.33, P = 0.26; TC vs. CC: OR = 1.23, 95 % CI = 0.84-1.82, P = 0.29; TT/TC vs. CC: OR = 1.28, 95 % CI = 0.89-1.84, P = 0.19). In the subgroup analysis base on the ethnicity, the results suggested that MTHFR C677T polymorphism was significantly associated with thyroid cancer risk both in Caucasian and Asian populations in recessive model: (Caucasians: TT vs.
Tc/cc: OR = 2.28, 95 % CI = 1.11-4.67, P = 0.025; Asians: TT vs.
Tc/cc: OR = 1.86, 95 % CI = 1.57-2.20, P = 0.00). In conclusions, our meta-analysis suggested that the MTHFR C677T polymorphism is associated with thyroid cancer both in Caucasians and Asians.