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Background: Breast cancer is the most common cause of cancer-related death in women worldwide. Novel genetic markers for breast cancer susceptibility have been identified in population-based studies. The aim of this study was to examine the association of two single-nucleotide polymorphisms (SNPs) of FGFR2 (rs1219648) and TOX3 (rs8051542) with the risk of breast cancer in Iranian women. Methods: Breast cancer patients (n?=?126) and healthy controls (n?=?160) were genotyped for SNPs in FGFR2 (rs1219648) and TOX3 (rs8051542) using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Also, immunohistochemical tests for human epidermal growth factor receptor-2, estrogen receptor, and progesterone receptor were carried out on breast tumor tissues. Results: TOX3 (rs8051542) CC (OR?=?1.24; 95% CI, 0.72-0.214; P?<?0.001) and FGFR2 (rs1219648) GG (OR?=?62.0; 95% CI, 23.63-162.66; ?2?=132.775?; P?<?0.001) polymorphism was significantly associated with breast cancer. The association was also significant between breast cancer risk and TOX3 (rs8051542) TC and FGFR2 (rs1219648) AG variants. Conclusion: Our findings suggested that genetic variants of FGFR2 (rs1219648 AG) and TOX3 (rs8051542 TC) can be potential candidate biomarkers for breast cancer risk.