Voltage‐gated sodium channels (Nav) are essential for the initiation and propagation of action potentials in neurons. Nav1.8 activity is regulated by prostaglandin E2 (PGE2). There is, however, no direct evidence showing the regulated trafficking of Nav1.8, and the molecular and cellular mechanism of PGE2‐induced sodium channel trafficking is not clear. Here, we report that PGE2 regulates the trafficking of Nav1.8 through the protein kinase A (PKA) signaling pathway, and an RRR motif in the first intracellular loop of Nav1.8 mediates this effect. In rat dorsal root ganglion (DRG) neurons, prolonged PGE2 treatment enhanced Nav1.8 currents by increasing the channel density on the cell surface. Activation of PKA by forskolin had the same effect on DRG neurons and human embryonic kidney 293T cells expressing Nav1.8. Inhibition of PKA completely blocked the PGE2‐promoted effect on Nav1.8. Mutation of five PKA phosphorylation sites or the RRR motif in the first intracellular loop of Nav1.8 abolished the PKA‐promoted Nav1.8 surface expression. Furthermore, a membrane‐tethered peptide containing the intracellular RRR motif disrupted the PGE2‐induced promotion of the Nav1.8 current in DRG neurons. Our data indicate that PGE2 promotes the surface expression of Nav1.8 via an intracellular RRR motif, and provide a novel mechanism for functional modulation of Nav1.8 by hyperalgesic agents.