Objective?To investigate the correlations of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and its enzyme metabolites with senile cataract.?Methods?A total of 663 patients with senile cataract in Mianyang Central Hospital from January 2019 to June 2020 were collected as the study group, and 646 healthy subjects were randomly selected as the control group in the same period.?MTHFR?gene polymorphism i.e., CC, CT or TT genotypes and the levels of serum homocysteine (HCY), folic acid (FOL), vitamin B12?(VitB12) and vitamin B6?(VitB6) were detected respectively. Multiple Logistic regression was used to analyze the correlation between each parameters and senile cataract.?Results?The mutation rate of?MTHFR?C677T (χ2=24.910,?P<0.001) and HCY levels (Z=17.104,?P<0.001) in the study group were significantly higher than those in control group, while the levels of FOL (Z=-11.695,?P<0.001), VitB12?(Z=-10.903,?P<0.001) and VitB6?(Z=-7.646,?P<0.001) were significantly lower. With the increase of?MTHFR?C677T mutation i.e., CC→CT→TT, HCY level showed an upward trend (Z=7.653 and 8.266, both?P<0.001) while FOL level (Z=-5.212 and -10.634, both?P<0.001) and VitB12?(Z=-2.226 and -3.069, both?P<0.001) showed a decreased trend in both of study group and control group. Multiple Logistic regression analysis showed that the levels of HCY (OR=1.24 and 1.18, both?P<0.001) and FOL (OR=0.95 and 0.91, both?P<0.001) were associated with senile cataract and?MTHFR?mutations. VitB12?was only associated with senile cataract (OR=0.86,?P=0.001). Compared with CC genotype, in the patients with CT (OR=1.62,?P<0.01) and TT (OR=1.76,?P<0.01) genotype the risk of senile cataract increased.?Conclusion?Monitoring?MTHFR?gene polymorphism and the changes of serum HCY, FOL and VitB12?levels may be of reference value in predicting senile cataract.