Objective: To explore and analyze the polymorphism of MTHFRC677T gene in ischemic stroke population of Han nationality in Yunfu area. Methods: A total of 100 Han patients with ischemic stroke who underwent genetic testing for stroke risk in the hospital from January 2018 to October 2019 in Yunfu area were recruited. A total of 100 health volunteers were taken as controls. The polymorphism of MTHFRC677T gene in ischemic stroke population of Han nationality in Yunfu area was investigated. Results: Compared with the control group, the TT homozygous genotype frequency and T allele frequency of MTHFRC677T gene variation in Yunfu Han population with ischemic stroke were significantly increased, and the Hcy index level of TT genotype in patients with ischemic stroke was significantly higher than that of CC and CT genotype. Conclusion: The mutation probability of MTHFRC677T gene in Yunfu Han population with ischemic stroke is high. Among the polymorphisms of MTHFRC677T gene, TT genotype can induce increased plasma Hcy level, which can be a high risk factor for ischemic pawns.