The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells ( P<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 μmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines ( P<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level ( P<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells ( P<0.05) and a decrease in G2/M-phase cells ( P<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression ( P<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.