Nociceptive-selective analgesia is often preferred over traditional methods, providing effective pain relief with minimum systemic side effects.The quaternary lidocaine derivative QX-314, is a promising local anesthetic for achieving selective analgesia. However, due to its inability to penetrate the cell membrane, its efficacy is limited to intracellular administration. In this study, we aimed to develop an injectable electrospun fiber-hydrogel composite comprising QX-314-loaded poly(ε-caprolactone) electrospun fiber and capsaicin (Cap)-loaded F127 hydrogel (Fiber-QX314/Gel-Cap composite) for long-term and nociceptive-selective analgesia. The sequential and sustained release mechanism of Cap and QX-314 helped remarkably extend the sensory blockade duration up to 44.0 h, and prevent motor blockade. Specifically, our findings indicated that QX-314 can traverse the cell membrane through the transient receptor potential vanilloid 1 channel activated by Cap, thus targeting the intracellular Na+ channel receptor to achieve selective analgesia. Moreover, the composite effectively alleviated incision pain by suppressing c-Fos expression in the dorsal root ganglion and reducing the activation of glial cells in the dorsal horn of the spinal cord. Consequently, the Fiber-QX314/Gel-Cap composite, designed for exceptional biosafety and sustained selective analgesia, holds great promise as a non-opioid analgesic.