Fibroblast Growth Factor Homologous Factors (FHFs) are cytosolic members of the of the FGF proteins. Four members of this subfamily (FHF1-4) are differentially expressed in multiple tissues in an isoform-dependent manner. Mutations in FHF proteins have been associated with multiple neurological disorders. FHF proteins bind to the C-terminus of voltage-gated sodium (Nav) channels and regulate current amplitude and gating properties of these channels. FHF2, which is expressed in DRG neurons, has two main splicing isoforms, FHF2A and FHF2B, which differ in the length and sequence of their N-termini, have been shown to differentially regulate gating properties of Nav1.7, a channel that is a major driver of DRG neuron firing. FHF2 expression levels are downregulated following peripheral nerve axotomy, which suggests that they may regulate neuronal excitability via an action on Nav channels after injury. We have previously shown that knockdown of FHF2 leads to gain-of-function changes in Nav1.7 gating properties: enhanced repriming, increased current density and hyperpolarized activation. From this we posited that knockdown of FHF2 might also lead to DRG hyperexcitability. Here we show that knockdown of either FHF2A alone or all isoforms of FHF2 results in increased DRG neuron excitability. In addition, we demonstrate that supplementation of FHF2A and FHF2B reduces DRG neuron excitability. Overexpression of FHF2A or FHF2B also reduced excitability of DRG neurons treated with a cocktail of inflammatory mediators, a model of inflammatory pain. Our data suggest that increased neuronal excitability after nerve injury might be triggered, in part, via a loss of FHF2-Nav1.7 interaction.