Abstract: 【Abstract】 Objective To explore the association of CD44 rs4756195 polymorphisms with genetic susceptibilities and clinico-pathologic characteristics to breast cancer of Han Nationality in Chongqing, China. Methods This case-control study included 170 patients with breast cancer and 178 healthy controls, single nucleotide polymorphisms (SNPs) of CD44 rs4756195 polymorphisms at intron 1 were genotyped by Sequenom MassArray iPLEX GOLD System. Data was analyzed via t test, Chi-square test and Logistic regression analysis. Results The frequencies of genotypes (AA, AG and GG) of CD44 rs4756195 showed a significant difference in the distribution of the genotypes between patients with breast cancer and healthy controls （χ2=6.272，P=0.043）. The GG and AG genotype significantly increased the risk of breast cancer compared with AA genotype （OR=6.035，95%CI：1.262-28.856，P=0.024；OR=5.367，95%CI：1.166-24.709，P=0.031）. The rate of axillary lymph nodes metastasis in patients with breast cancer who carried with GG genotype was higher than those carried with AG and GG genotype （62.6% vs. 44.7%, χ2=4.473，P=0.034）. The positive rate of CD44 in patients with breast cancer who carried with AG and GG genotype was higher than those carried with GG genotype （68.1 % vs. 45.5%，χ2=6.930，P=0.008）. Conclusion CD44 rs4756195 polymorphisms are closely associated with the increased risk for breast cancer in Han Nationality; AG and GG genotype are susceptible genotype for breast cancer. CD44 rs4756195 polymorphisms are closely associated with the expression of CD44 and axillary lymph nodes metastasis, the patients with breast cancer who carried with GG genotype may have bad prognosis.