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Background Recent studies have suggested that susceptibility to major depressive disorder (MDD) might be related to the serotonin 1A receptor (5-HTR1A) C(-1019)G polymorphism. In this study, we aimed to assess the association between 5-HTR1A C(-1019)G polymorphism and MDD in the North Hart ethnic group of China.Methods The C(-1019)G of 5-HTR1A was detected with polymerase chain reaction (PCR) in 400 patients with MDD and 400 unrelated age-and sex-matched healthy control subjects. Association between the C(-1019)G and MDD was statistically analyzed.Results There was a statistically significant difference between MDD patients and controls in both the genotype distribution (X2=10.913, df=2, P=0.004) and the allele frequency (X2=10.379, dr=l, P=0.001), and a significant difference in the genotype distribution and the allele frequency was found both in the female subjects (Genotype distribution:X2=15.406, df=2, P=0.000; allele frequency: X2=15.552, df=l, P=0.000) and the late-onset subjects (Genotype distribution:X2=7.771, df=2, P=0.021; allele frequency: X2=8.007, df=l, P=0.005) in the two groups.Conclusion These results suggest that 5-HTR1A C(-1019)G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD.