Voltage-gated sodium channel Na(V)1.7 serves as an attractive target for chronic pain treatment. Several venom peptides were found to selectively inhibit Na(V)1.7 but with intrinsic problems. Among them, Ssm6a, a recently discovered centipede venom peptide, shows the greatest selectivity against Na(V)1.7, but dissociates from the target too fast and loses bioactivity in synthetic forms. As a disulfide-rich venom peptide, it is difficult to optimize Ssm6a by artificial mutagenesis and produce the peptide with common industrial manufacturing methods. Here, we developed a novel protein scaffold fusion strategy to address these concerns. Instead of directly mutating Ssm6a, we genetically fused Ssm6a with a protein scaffold engineered from human muscle fatty acid-binding protein. The resultant fusion protein, SP-TOX, maintained the selectivity and potency of Ssm6a upon Na(V)1.7 but dissociated from target at least 10 times more slowly. SP-TOX dramatically reduced inflammatory pain in a rat model through DRG-targeted delivery. Importantly, SP-TOX can be expressed cytosolically in Escherichia coli and purified in a cost-effective way. In summary, our study provided the first example of cytosolically expressed fusion protein with high potency and selectivity on Na(V)1.7. Our protein scaffold fusion approach may have its broad application in optimizing disulfide-rich venom peptides for therapeutic usage.