〔Abstract〕 Objective To investigate the expression of SENEX in diffuse large B-cell lymphoma(DLBCL) and its effect on the recurrence of DLBCL and its possible mechanism. Methods Western blot and qRT-PCR were used to detect SENEX gene and protein expression in 3 patients with newly diagnosed DLBCL(newly diagnosed group), 3 patients with relapsed DLBCL(recurrent group) and 3 patients with complete remission of DLBCL(complete remission group). SENEX in DLBCL cell OCI-LY8 were silenced with SiRNA transfection technology and the efficiency of transfection was verified by Western blot and qRT-PCR. The cell proliferation was measured by the CCK-8 analysis. The concentration of free transcription factor binding to the adenovirus E2 promoter(E2 F) in cell supernatant was measured by ELISA. Western blot was used to detect expression of p16 and retinoblastoma(Rb)/phosphorylation retinoblastoma(pRb). Results SENEX and protein levels increased significantly in patients with relapsed DLBCL; SENEX expression in silencing DLBCL cells inhibited the proliferation of DLBCL cells, E2 F activation and Rb activation. Conclusion The SENEX gene promotes proliferation and recurrence of DLBCL by activating the Rb/E2 F1 pathway.