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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in the world. It exhibits high heterogeneity and invasiveness and is prone to developing treatment resistance. Therefore, there is an urgent need for good prognostic evaluation indicators and therapeutic targets. In recent years, immunotherapy has become a research hotspot for DLBCL. Tumor-associated neutrophil (TAN) is widely expressed in various tumors and is an important component of the immune microenvironment. However, there have been few studies on the role of TAN in DLBCL. This study has demonstrated that CD66b, which is a marker of TAN, is a good prognostic marker of DLBCL and its expression is related to the prognosis of DLBCL patients. The expression level of CD66b is also closely correlated with the objective response rate of the R-CHOP treatment regimen in DLBCL patients with non-GCB subtype. The expression level of CD66b has a high reference value for the determination of the treatment plan. The combined detection of CD66b and PD-L1/PD-L2 is of significance to predict the prognosis of DLBCL patients.