Previous work suggests that the methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphism A1298C may be a risk factor for schizophrenia. In this study, the genetic association between the MTHFR A1298C polymorphism and schizophrenia was investigated in 379 patients with schizophrenia and 380 age- and sex-matched controls subjects. The results showed an association between the 1298C allele and the disorder (OR 1.39, 95% confidence interval 1.08-1.79). This provides further evidence that the MTHFR A1298C polymorphism may play a role in conferring risk for schizophrenia in the Chinese Han population.