The purpose of this study was to investigate the association between the metabotropic glutamate receptor 3 (GRM3) subunit gene and alcohol dependence by the single-nucleotide polymorphisms (SNPs).Two hundred and forty-eight male alcohol-dependent patients and 235 male control subjects were recruited. Ten SNPs in the GRM3 region were studied, and genotyping of SNPs was performed by ligase detection reactions.We found highly significant differences in allele and genotype frequencies of rs6465084 between the alcohol-dependent and control group, with the greater frequency of A allele of SNP rs6465084 in alcohol-dependent group. We also found significant differences of haplotype frequencies in five combinations (including TAATATT, CAGTATT, TCGTATT, CAATAGC, TAATATC) in the linkage disequilibrium constructed by seven SNPs between the groups.Our results supplied the first evidence that the polymorphism of GRM3 gene associates with the morbidity of alcohol dependence in human being, which may support a new potential target for alcoholism treatment.