〔Abstract〕 Objective To investigate the role and mechanism of cellular senescence in diffuse large B cell lymphoma(DLBCL) cells resistance to chemotherapy. Methods DLBCL patients in the group were divided into Newly Diagnosed(ND) group, Complete remission(CR) group, relapsed/refractory(r/r) group.HE staining and senescence β-galactosidase staining were used to detect the senescence of lymphatic tissue in the lymph node reactive hyperplasia patients and the r/r DLBCL patients; senescence β-galactosidase staining was used to detect the peripheral blood of DLBCL patients in the ND group and the r/r group; the expression of inflammatory factors in serum of DLBCL patients was detected by ELISA;an senescence model was constructed by repetitively induce senescence of DLBCL cell line LY8 with 10,20,and 40 nmol/L doxorubicin(DOX);CCK-8 was used to detect the cell proliferation of senescent model.Flow cytometry was used to detect the apoptosis of senescent model.ELISA was used to detect cytokine expression in serum of DLBCL patients and supernatant of senescence model. Results Senescent cells in lymph node tissues and peripheral blood of r/r DLBCL patients significantly increased, and the secretion of pro-inflammatory and immunosuppressive cytokines such as interleukin-6(IL-6),interleukin-8(IL-8),interleukin-10(IL-10),interleukin-35(IL-35) and transforming growth factor β1(TGF-β1) in serum increased; 40 nmol DOX was used to induce senescence of LY8 cells, and the proportion of senescent cells was 24.77%.The function detect of control group and DOX induced group showed that the cell proliferation rate of the senescence group was lower than that of the control group but higher than that of the 10 nmol/L and 20 nmol/L DOX groups(P<0.05);The apoptosis rate was higher than the control group but lower than the 10 nmol/L and 20 nmol/L DOX groups(P<0.05).Meanwhile, IL-2,IL-6,IL-8,IL-10,TGF-β1 secretion levels in each group were significantly different(P<0.05).Compared with the control group, the secretion of various pro-inflammatory and immunosuppressive cytokines such as IL-2,IL-6,IL-8,IL-10,IL-35,TGF-β1 in the supernatant of the senescent group increased. Conclusion Cellular senescence promotes DLBCL cell apoptosis resistance by inducing inhibitory cytokine accumulation.