Abstract: Diffuse large B-cell lymphoma(DLBCL) is the most common form of lymphoma that accounts for 30% to 40% of all lymphomas among adults.The clinical outcomes are extremely varied, with five-year survival rates between 30% and 80%, which are widely dependent on clinical risk factors and biological heterogeneity.Based on biological heterogeneities, DLBCL can be divided into different subgroups, such as germinal center B-cell-like(GCB) DLBCL, activated B-cell-like(ABC) DLBCL, and primary mediastinal B-cell lymphoma(PMBL).The five-year survival rates of GCB-DLBCL and ABC-DLBCL are 59% and 30%, respectively.The rituximab-combined CHOP(RCHOP) regimen has significantly improved the overall survival of DLBCL patients.However, a number of patients remain resistant to rituximab or undergo relapse after rituximab treatment.We studied the relationship between the expression level of cell division cycle 7(CDC7) protein and the survival rate of 60 DLBCL patients in a previous study.After they received RCHOP chemotherapy, the median survival time of patients with low CDC7 expression was higher than those with high CDC7 expression(P=0.027).Higher expression of CDC7 was observed among ABC-DLBCL patients(21/28, 75.0%).Overall, we speculate that the CDC7/ phospharylated minute chromosome maintenance protein 2(pMCM2) signal pathway has an important role in chemotherapy resistance.CDC7 can also be a potential therapeutic target in DLBCL, especially for ABC-DLBCL.The in vitro culture system and tumor-transplanted nude mice model are used in this study to examine CDC7 gene expression.CDC7 gene expression are inhibited and enhanced in this study to clearly identify the relationship between the CDC7/pMCM2 signal pathway and the survival of DLBCL cells.Furthermore, we explore relevant clinical significance focused on the potential use of novel molecular targeting strategies against DLBCL, especially for ABC-DLBCL.