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Introduction: Metalloproteinases and their tissue inhibitors play an important role in the metastases formation. A multistage process of carcinogenesis requires the involvement of numerous enzymes and compounds that facilitate the expansion of tumor cells. The formation of metastases depends on both metalloproteinases and tissue inhibitors activation leading to the activation of neoangiogenesis. The changes of the expression in stromal and tumor proteins could be prognostic factors in patients with oropharyngeal squamous cell carcinoma. Materials and Methods: This study was conducted on a total of 34 patients with squamous cell carcinoma of the oropharynx divided into 2 groups, including 20 patients with neck metastasis and 14 patients without lymph node metastasis. Immunohistochemistry was performed with a standard protocol. Results: The results of the present analysis indicated a higher expression of metalloproteinases 2 in the stroma than in tumor with increasing tumor grade. The dynamics of changes in the expression of metalloproteinases showed the increase in metalloproteinases 2 and the decrease in metalloproteinases 9 depending on the tumor size. Dynamics of changes in the expression of tissue inhibitor 1 in the tumor stroma significantly increased with the tumor stage. In the assessment of nodal staging from N0 to N3, the expression of tissue inhibitor 1 and 2 were higher in the tumor tissues. The increase of metalloproteinases 2, tissue inhibitor 1 in the tumor, and metalloproteinases 9 in the stroma were characterized by a reduction in the odds ratio of patient’s survival. Conclusion: The complex evaluation of the expression of metalloproteinases and tissue inhibitors may be used for the prognosis of the patient’s survival.