Objective To explore the relationship between DNA methyctransferace1(DNMT1)gene polymorphism and cognitive function in the first episode, drug-na?ve schizophrenia. Methods One hundred eighty-six first episode, drug-na?ve schizophrenia patients and 182 healthy controls were examined by using polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining to determine genotype and allele of DNMT1 gene. Cognitive function was assessed by using the standardized measurement tools—the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Chinese version. Comparisons were made on the cognitive function and the genotype and allele distribution of SNP rs2114724 and rs2228611 between schizophrenia group and the control group.The relationship between DNMT1 gene polymorphism and cognitive function was analyzed. Results There was no significant difference of the genotype T/T, T/C, C/C and allele T, C distribution of SNP rs2114724 between schizophrenia group and healthy controls group (P>0.05). There was no significant difference of the genotype G/G, G/A, A/A and allele G, A distribution of SNP rs2228611 between schizophrenia group and healthy control group (P>0.05). There was significant difference in Spatial Span Test (SST) scores(P<0.05)among three different genotype T/T,T/C and C/C of rs2114724 in schizophrenic group.The SST scores of the patients with C/C genotype were higher than that of the patients with T/T or T/C genotype (P<0.05). Conclusion DNMT1 gene polymorphisms is not associated with the first-episode, drug-na?ve schizophrenia, but may be associated with the work memory in cognitive function of schizophrenia in the Chinese Han population.