Objective[|]P53, Bcl-2, and Fas proteins play significant roles in lymphoid cell apoptosis. These proteins affect the prognosis and treatment response of lymphoma and various malignancies. The aim of the present study was to investigate the effects of P53, Bcl-2, and Fas protein expression on treatment and prognosis in patients with primary gastrointestinal diffuse large B-cell lymphoma.[¤]Materials and Methods[|]Thirty-nine patients with primary gastrointestinal diffuse large B-cell lymphoma were included in the study. Immunohistochemical staining was performed to analyze P53, Bcl-2, and Fas protein expression levels in paraffin sections.[¤]Results[|]We examined 39 patients with primary gastrointestinal diffuse large B-cell lymphoma, 21 males and 18 females, with a median age of 54 years. P53 protein expression was detected in 24 patients (61.5%), Bcl-2 protein expression was detected in 26 (67%), and Fas protein expression was detected in 28 (72%). The five-year overall survival rate was significantly lower in patients with P53 and Bcl-2 expression; on the other hand, we did not find a significant difference in the five-year overall survival with respect to Fas protein expression.[¤]Conclusion[|]We found that P53 and Bcl-2 protein expression had a negative effect on prognosis and survival in patients with primary gastrointestinal diffuse large B-cell lymphoma. However, Fas protein expression had no effect on prognosis and survival. Taken together, patients with P53 and Bcl-2 expression should be considered to have a high risk from the beginning, and these patients should undergo aggressive treatments.[¤]