Objective:To detect A20 mutation and to investigate its relationship with clinicopathologic features, prognosis, and re-sistance to therapy of diffuse large B cell lymphoma (DLBCL). Methods:A total of 104 cases with DLBCL and their clinical data were collected;follow-up was performed on a few of DLBCL patients. The expression of P-gP and Ki-67 protein was detected with immuno-histochemical staining. The A20 gene mutation in exons 3, 6, and 7 were examined by polymerase chain reaction and DNA sequencing. Finally, the correlation of genetic abnormality of A20 with clinicopathologic features was analyzed. Results:Missense mutation in ex-on 3 of A20 gene was identified in 18 of 104 patients (17.3%). The A20 gene mutation at site 73 of exon 3 was greater in the cases with activated B cell-like-DLBCL than with germinal center B-cell-like-DLBCL (18.5%vs. 2.5%, P=0.010). In contrast to the advanced clin-ical stage and high International Prognostic Index (IPI) cases, the rate of A20 mutation was superior to the opposite (P<0.05). The ex-pression for P-gP was higher in the cases with mutation than that of those with wild-type A20 gene (16/18 vs. 52/86, P=0.021). The dif-ference in A20 mutation between the groups of low and high positive expression for Ki-67 (1/17 vs. 26/60, P=0.030) was significant. DLBCL with A20 mutation had an increasing recurrence tendency (P=0.06) and a worse survival (P=0.016) compared with those with wild-type A20 gene. Conclusion:The A20 mutation has a certain influence on the clinicopathologic characteristics and survival condi-tions of BLBCL patients. Probably, A20 mutation is a factor associated with a poor prognosis of DLBCL.