There are increasing evidences that HSD17B1 plays a significant role in the development of breast cancer. However, published data on the association between HSD17B1 Ser312Gly polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of this relationship, a meta-analysis including 9 studies with 31,053 subjects was performed in this study. Crude ORs with 95% CIs were used to assess the strength of association between HSD17B1 Ser312Gly polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (Gly/Gly versus Ser/Ser, Gly/Ser versus Ser/Ser), dominant model (Gly/Gly + Gly/Ser versus Ser/Ser), and recessive model (Gly/Gly versus Gly/Ser + Ser/Ser), respectively. Overall, no significant associations were detected between HSD17B1 Ser312Gly polymorphism and breast cancer susceptibility. However, in the stratified analysis by ethnicity, significant associations were observed in Caucasians for Gly/Gly versus Ser/Ser (OR = 0.91; 95% CI 0.83-1.00), Gly/Ser versus Ser/Ser (OR = 0.92; 95% CI 0.85-0.99), and Gly/Gly + Gly/Ser versus Ser/Ser (OR = 0.92; 95% CI 0.86-0.98). In conclusion, this study suggests that HSD17B1 312Gly allele may be a protective factor for breast cancer development in Caucasians. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.