Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) of rs2279744 locus in the promoter region of mouse double minute 2 homolog (MDM2) gene and risk of breast cancer. Methods: Case-control studies regarding the association between the SNPs of MDM2 rs2279744 locus and risk of breast cancer were collected by searching several national and international databases. The eligible studies were screened out according to the criteria. Meta-analysis was performed following data extraction, and the sensitivity and publication bias were also analyzed. Results: Twenty-eight case-control studies were included, with 11 804 breast cancer patients in case group and 152 09 subjects in control group. The results of Meta-analysis showed that there were significant differences in mutant genotype and wild genotype (TG/GG vs. TT) as well as in alleles (G vs. T) in the overall population (OR=1.15, 95% CI=1.06–1.24, P<0.001; OR=1.12, 95% CI=1.05–1.18, P<0.001); subgroup analysis divided by different continents reveal that those differences only found in Asia’s population (TG/GG vs. TT: OR=1.34, 95% CI=1.15–1.57, P<0.001 by random effects model, OR=1.34, 95% CI=1.20–1.50, P<0.001 by fixed effect model; G vs. T: OR=1.21, 95% CI=1.09–1.35, P=0.001 by random effects model). The sensitivity analyses and Egger’s tests verified the reliable conclusions and no obvious publication biases. Conclusion: Asian individuals with mutant genotype homozygote (GG) and heterozygous (TG) in MDM2 rs2279744 locus have a higher risk of breast cancer than those with wild genotype (TT). Mutations in MDM2 rs2279744 locus are closely associated with the risk of breast cancer in Asians.