Abstract： Objective To investigate the clinical significance of MTAP, CDKN2A and CDKN2B gene expression in diffuse large B-cell lymphoma (DLBCL). Methods MTAP, CDKN2A and CDKN2B gene expression were assessed by Real-time quantitative PCR in 40 cases of DLBCL and 19 cases of reactive hyperplasia. The clinical and follow-up data were also collected. Results Comparing with reactive hyperplasia, MTAP, CDKN2A and CDKN2B gene expression were decreased in DLBCL group (P = 0.024,0.044 and 0.047, respectively). Low-expression of all the three genes were associated with advanced Ann Arbor stage (P=0.004, 0.001 and 0.027, respectively). No obvious difference were observed according to gender, age, the number of the extra-nodal infiltration, ECOG score, bone marrow involvement and serum LDH level (P ＞0.05). MTAP and CDKN2A gene expression were associated with B symptoms (P =0.003 and 0.028, respectively) and IPI scores (P =0.001 and 0.011, respectively). With regard to survival rates,MTAP, CDKN2A and CDKN2B gene expression were significantly associated with OS (P =0.022, 0.019 and 0.042, respectively). Conclusion MTAP, CDKN2A and CDKN2B gene expression in DLBCL were decreased and related to disease progression and prognosis. They could be considered as biomarkers to evaluate biological behavior and clinical outcome of DLBCL patients.