Background. Different factors are involved in the incidence, etiology, metastasis, diagnosis, and treatment of oral squamous cell carcinoma, including apoptosis inhibitor proteins. Baculoviral IAP repeat containing protein 6 (BIRC6) is one of the apoptosis inhibitor proteins contributing to cancer cells’ survival in many cancer types with diagnostic and treatment importance. This study is aimed at assessing the serum level of BIRC6 in oral squamous cell carcinoma. Materials and Methods. In this retrospective cross-sectional study, 60 serum samples were collected from 45 male and 15 female patients with a mean age of 61 years as the case group and 28 serum samples of healthy people as a control group. The serum samples were analyzed using a commercial sandwich ELISA kit. Results. There were no significant differences between BIRC6 serum levels in patients and healthy subjects. Moreover, we did not observe any significant relationships between BIRC6 serum levels and the patients’ demographic or clinical characteristics. Conclusions. There was no significant difference in serum BIRC6 levels in patients with oral squamous cell carcinoma and healthy individuals. Its use in determining the prognosis of squamous cell carcinoma or considering it a determinant marker in this type of cancer may not have a place. More in-depth studies for evaluating BIRC6 serum levels in oral squamous cell carcinoma patients are recommended for better insight into this protein’s role in diagnosing, progression, and prognosis of the disease.