Several genome-wide association studies on breast cancer have reported similar findings of a new cancer susceptibility locus, 8q24 rsl3281615. Subsequent case-control studies have rapidly investigated the association between the single nucleotide polymorphism of rsl3281615 at chromosome 8q24 and breast cancer risk, but the effect of 8q24 rsl3281615 polymorphism on breast cancer is still unclear due to the inconsistence among those studies. Given the contradictory findings, a meta-analysis was performed to determine the association between 8q24 rsl3281615 polymorphism and breast cancer risk. 12 eligible case-control studies with a total of 42,508 cases and 53,928 controls were finally included into this meta-analysis by searching the PubMed, Embase, and China Biology Medicine (CBM) databases. We estimated the summary odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to assess this association. Meta-analyses of total 12 studies showed 8q24 rsl3281615 polymorphism was significantly associated with an increased risk of breast cancer in all contrast models (OR(G vs. A) = 1.10, 95 % CI 1.05-1.14, P (OR) < 0.001; OR(GG vs. AA) = 1.20, 95 % CI 1.11-1.29, P (OR) < 0.001; OR(AG vs. AA) = 1.08, 95 % CI 1.05-1.12, P (OR) < 0.001; OR(GG vs. AA +AG) = 1.13, 95 % CI 1.07-1.19, P (OR) < 0.001; OR(GG+AG vs. AA) = 1.13, 95 % CI 1.07-1.19, P (OR) < 0.001). Meta-analyses of studies with high quality showed that 8q24 rsl3281615 polymorphism was still significantly associated with an increased risk of breast cancer under the five genetic contrast models. Sensitivity analyses by sequential omission of any individual studies and subgroup analyses by ethnicity further identified the significant association between 8q24 rsl3281615 polymorphism and breast cancer risk. Conclusively, this meta-analysis shows a significant association between 8q24 rsl3281615 polymorphism and breast cancer risk.