Introduction: Diffuse large B-cell non- Hodgkin lymphoma (DLBCL) is the largest common category of adult lymphoma. Recurrence and treatment resistance occurs in one-third of cases, triggering them to the progressive stage of DLBCL after treatment. Detection of novel predictive and prognostic biomarkers leads to improvement of its treatment and prognosis. Aim of the study: To assess the prognostic roles of protein expression of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) in tissues of DLBCL patients. Material and methods: In the current study we included tissues from 100 cases of DLBCL. For immunohistochemistry, tissues were stained with MYD88 and TBLR1. We followed patients for about 3 years, and then we correlated their expression with clinicopathological and prognostic parameters. Results: Higher MYD88 and TBLR1 expressions were associated with presence of B symptoms, fever, night sweat, advanced stage, bone marrow involvement and bulky nodal size, presence of extra-nodal extension, unfavourable relapse-free survival, and unfavourable overall survival rates (p < 0.001). Conclusions: overexpression of MYD88 and TBLR1 expression was present in DLBCL patients and was associated with unfavourable clinicopathological and prognostic parameters.