Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and has a poor prognosis. The breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes are the key tumor suppressor genes responding in the cases of DNA damage. They repair double-strand DNA breaks to maintain gene stability. Mutations in BRCA1 and BRCA2 lead to genetic instability and develop different cancers, mainly familial breast and ovarian cancers. This study aimed to investigate the expression profiles of BRCA1 and BRCA2 genes in OSCC through the use of immunohistochemistry (IHC) technique. Method: In this retrospective study, a total of 60 samples (20 samples of each grade) were collected from the archive of pathology department of Taleghani educational hospital, Tehran, Iran, from 2000-2017. IHC staining was performed for all tissue samples. Results: BRCA1 immunoreactivity was positive in the cytoplasm and nuclear of 56 and 24 samples, respectively. None of the cancer cells showed nuclear BRCA2 expression; however, BRCA2 cytoplasmic staining existed in 17 cases. Chi-square test showed statistically significant differences between BRCA1 staining (P=0.001) and histological grade, and between BRCA2 expression (P=0.001) and histological grade in the research groups. Conclusion: Altered subcellular localization of BRCA1/2 and immunostaining of the cancer cells at the invasive front may indicate the critical role of BRCA1/2 in the development of OSCC. Early detection of BRCA mutation carriers by IHC has a significant impact on successful treatment.