The regulation of neutrophil half‐life by members of the coagulation cascade is critical for the resolution of the inflammatory response. We have demonstrated that soluble fibrinogen (sFbg) delays human neutrophil (PMN) apoptosis through a mechanism that involves CD11b interactions, and phosphorylation of focal adhesion kinase (FAK) and extracellular signal‐regulated kinase 1/2 (ERK1/2).Since NF‐κB is a key element in the regulation of apoptotic mechanisms in several immune cells, we investigated whether NF‐κB is involved in the control of PMN survival by sFbg. We showthat sFbg triggers inhibitor protein κB (IκB‐α) degradation and NF‐κB activation. Furthermore, pharmacological inhibition of NF‐κB abrogates sFbg effects on apoptosis. In addition, specific inhibition of MAPK ERK1/2 significantly reduces NF‐κB translocation by sFbg, suggesting a relationship between ERK1/2 and NF‐κB activation. Similar results are obtained when granulocytic‐differentiated HL‐60 cells are treated with sFbg, making this model highly attractive for integrin‐induced gene expression studies. It can be concluded that NF‐κB participates in the prevention of apoptosis induced by sFbg with the participation of MAPK ERK1/2. These results shed light on the molecular mechanisms that control human granulocyte apoptosis, and suggest that NF‐κB regulation may be of benefit for the resolution of the inflammatory response.