The aims of this study were to investigate FOXP1 expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL) and its association with the subclassification and other clinicopathologic parameters of DLBCL. Expression of FOXP1, CD10, Bcl6, MUM1, and Bcl2 was detected by immunohistochemistry on tissue microarray sections. The Kaplan-Meier method was used to estimate the overall survival of patients, and the log-rank test was used to compare survival differences between groups with different FOXP1 protein expressions. Expression of FOXP1 was detected in 67.4% (95/141) of DLBCLs. FOXP1 expression in non-GCB (67/90, 74.4%) was significantly higher than that in GCB (28/51, 54.9%) (p < 0.05). FOXP1 expression in MUM1-positive cases (62/81, 76.5%) was significantly higher than that in MUM1-negative cases (33/60, 55%) (p < 0.01). FOXP1 expression was positively correlated with Bcl2 (p < 0.05) in non-GCB among nodal DLBCL cases. Among the extranodal group, patients with FOXP1 expression had a significantly inferior OS compared to those with negative FOXP1 expression (p < 0.05), which was not seen in nodal group. In conclusion, FOXP1 expression might be involved in the tumorigenesis of both nodal and extranodal DLBCL. The most striking finding of this study was that FOXP1 expression had an adverse effect on survival of patients with extranodal DLBCL, which indicated that FOXP1 function might be mediated by different mechanisms in nodal and extranodal DLBCLs. FOXP1 might play a role in the pathogenesis of nodal non-GCB DLBCL through the pathways in which Bcl2 was involved, and it might be a second important biomarker for non-GCB.