Phosphorylation events act as a fine switch that regulates the proper functioning of the innate immune system upon IFN stimulation. Upon binding of IFN to its receptor, phosphorylation and activation of the Jak/STAT pathway is a very well studied event. However, little is known about the activation of other pathways and the role they play in modulating this powerful antiviral response. This led us to raise the hypothesis that, changes in the phosphorylation status of proteins induced by IFN stimulation can activate novel signaling pathways with an impact on the IFN response. To this end, we have conducted a label-free quantitative phosphoproteomic analysis and identified a new set of proteins that are modified upon IFN treatment, and thereby may represent novel candidates acting at different levels of the IFN response.