Abstract: Objective: To explore the correlation between rs854560 and rs757158 in paraoxophosphate 1 (PON1) gene and the genetic susceptibility to breast cancer (BC) in the female population in Guangxi.Methods: A total of 64 unrelated female healthy physical examination subjects without a family history of cancer (control group) and 60 female BC patients excluding other tumors and genetic diseases (BC group) from Guangxi were enrolled.2 mL EDTA-K₂ anticoagulant venous blood samples of all participants based on morning fasting were collected, and whole-genome DNA was extracted from whole blood samples of both groups.Single nucleotide polymorphisms (SNPs) of rs854560 and rs757158 in PON1 gene were detected in 64 healthy controls and 60 BC patients.The differences of genotypes and allele distribution frequency of rs854560 and rs757158 in PON1 gene between the two groups were compared.Independent susceptibility and protection genotypes and alleles were screened by logistic regression analysis by adjusting for age, smoking history, alcohol consumption history, as well as ethnicity.The relative risk of the disease was expressed by odds ratio (OR) and 95% confidence interval (95% CI).The haplotype construction analysis of two SNP sites in PON1 in each group was performed by SHEsis online software.Results: Significant differences were identified in age, alcohol and smoking consumption between the control group and the BC group (P< 0.05), whereas no significant differences were reported in BMI and ethnic composition ratio (P> 0.05).No statistically significant differences were observed in the distribution frequency of genotypes and alleles of rs854560 and rs757158 in PON1 gene between the two groups (P> 0.05).The genotypes and alleles of rs854560 and rs757158 in PON1 gene were not associated with BC (P> 0.05), and the constructed haplotype AT had a 1.662-fold increase in the risk of BC (P< 0.05).Conclusion: Age, drinking and smoking consumption are the risk factors for BC.The two sites of rs854560 and rs757158 in PON1 gene are not associated with the risk of BC and other molecular subtypes in female population in Guangxi and the constructed haplotype AT of rs854560 and rs757158 in PON1 gene is associated with the risk of BC.Haplotype AT increases the risk of BC, and haplotype AT may be a genetic risk factor for BC in the female population in Guangxi.