In vivo analyzing chemical significance under human skin has impinged a formidable challenge upon regular optical methods due to its intrinsic opaque property. With analogy to a needle biopsy, conceptually and practically, here, we fabricated a “needle-like” nanopore-embellished TiO₂ column through electrochemistry directed etching, intriguingly serving as hundreds of thousands of liquid containers, perpendicular to the needle axle. A silver nanostructure synthesized in situ within the nanotube array gives rise to an opportunity for enhanced Raman detection to profile the extracts with excellent sensitivity and considerable spatial resolution, delineating the molecular information in depth. This SERS-active needle, which combined the functions of liquid biopsy and optical detection can penetrate the upper skin layer with minimal invasion and obviation of the extra step for the mass-limited sample transferring, unraveling the chemical insights underneath the opaque materials.