Objectives: To determine the expression of different isoforms of the gene BIRC5 in the tumor tissue of patients with oral and oropharyngeal squamous cell carcinoma compared to the tissue of healthy controls. To determine gene BIRC5 polymorphisms from blood samples of patients and healthy controls, and to compare their correlations as well as correlations with clinical pathohistological parameters. Study design: The research was designed as a retrospective study. Participants and methods: The study included patients with pathohistologically confirmed oral and oropharyngeal squamous cell carcinoma. As a control group, samples of buccal mucosa and peripheral blood of patients who were treated at the Department of Maxillofacial and Oral Surgery for some other non-malignant diseases were used. Genomic DNA was isolated from blood for analysis of polymorphisms by PCR, heteroduplex analysis and sequencing, and isoform expressions were determined by qPCR from total RNA of tumor samples and samples of healthy mucosa. Results: A total of eight isoforms of the BIRC5 gene were examined, whose relative expressions were found both in tumor tissue and in healthy control samples. All isoforms are statistically significantly more expressed in tumor tissue, with the most expressed isoforms being S wt, S 2α and S 2B. In comparison with the clinical and pathological parameters, the relative expression of the S Δex3 isoform in oropharyngeal lesions, as well as in advanced clinical stages (III and IV) of both tumor lesions, was statistically significant. Furthermore, a total of 17 polymorphisms were found, of which 11 appeared in tumors of the oral cavity and oropharynx with a minor allele frequency (MAF) greater than 5%. Conclusion: Survivin, the protein product of the BIRC5 gene, is a potential biomarker of aggressiveness or an indicator of the outcome of treatment in patients with oral and oropharyngeal squamous cell carcinoma. All isoforms of survivin are more strongly expressed in tumor tissues, and their expression generally cannot be corelate with clinical-pathological parameters, except isoform S Δex3. Five polymorphisms (c.-1547C>T, c.-31G>C, c.385G>A, c.*148T>C, c.*1373C>A) were significantly associated with tumor size, tumor stage and positive lymph nodes . The results show that these BIRC5 polymorphisms do not have a significant impact on patient survival and suggest for further research related to the expression of individual isoforms of this gene, such as the S Δex3 isoform, with the progression of HNSCC.