Objective — to determine the relationship between the immunohistochemical characteristics of tumor cells and their cellular microenvironment with varying degrees of differentiation of squamous cell carcinoma of the tongue. Material and methods. The investigation enrolled 59 cases of tongue squamous cell carcinoma; three groups were formed according to tumor grades (G1, G2, and G3). The expression of biological markers, such as p53, Ki-67, BCL-2, Cyclin D1, matrix metalloproteinase-9 (MMP-9), and CD82/KAI1, was studied in the tumor cells; B-lymphocytes (CD20), T-lymphocytes (CD8), NK cells (CD57), macrophages (CD68), plasma cells (CD138), the expression of tetraspanins (CD82/KAI1) and MMP-9 in the stromal cells, as well as capillary densities were examined in the tumor microenvironment. Results. Low-grade (G1) squamous cell carcinoma was found to have only a moderate correlation between the tumor microenvironment cells (CD57 lymphocytes and CD68 macrophages) (R=0.6; p=0.016); moderate-grade (G2) squamous cell carcinoma showed a weak positive correlation between the Ki-67 proliferative activity of tumor cells and their expression of CD82/KAI1 (R=0.39; p=0.023). The correlations between tumor cells and stromal cells were as follows: a weak negative correlation between tumor cells and the expression of p53 and CD82-positive stromal cells (R =–0.39; p=0.024); a weak positive correlation between the tumor cell expression of Cyclin D1 and CD20 B lymphocytes (R=0.36; p=0.036). In addition, there were correlations between the stromal cells: a weak positive correlation between CD20 B lymphocytes and CD8 T-lymphocytes (R=0.36; p=0.036), CD8 T-lymphocytes and CD68 macrophages (R=0.46; p=0.006), and CD57 NK cells and CD68 macrophages; a moderate correlation between CD8 T-lymphocytes and CD57 NK cells (R=0.57; p=0,000). In high-grade (G3) squamous cell carcinoma, there were a larger number of moderate correlations, as well as strong correlations between tumor cells and the expression of Cyclin D1 and MMP-9 (R=0.83; p= 0.006), between tumor cells and stromal components: the Ki-67 proliferative activity of tumor cells and capillary bed density (R=0.67; p=0.023), between tumor cells and the expression of CD82/KAI1 and CD82-positive stromal cells (R=0.717; p=0.012), CD8 T-lymphocytes (R=0.63; p=0.03), CD57 NK cells (R=0.64; p=0.032), CD68 macrophages (R=0.69; p=0.018), as well as correlations between the stromal cells: CD20 B lymphocytes and CD68 macrophages (R=0.71; p=0.013), CD8 T lymphocytes and CD57 NK cells (R=0.68; p=0.020), CD57 NK cells, and CD68 macrophages (R=0.76; p=0.000). Conclusion. The decrease in the grade of tongue squamous cell carcinoma is accompanied by increases in the number and strength of correlations between both the cells of a tumor and its microenvironment.