We report a method for the fabrication and selective functionalization of the internal and external surfaces of high-aspect-ratio hollow silicon dioxide (SiO2) micropillar arrays. The strategy enables independent surface reactions with no cross-contamination. The dual-functionalization is carried out during the fabrication of the micropillars in four steps. First, a sample of macroporous silicon is prepared by electrochemical etching and then it is thermally oxidized to create a thin layer of silicon dioxide on the internal surface of the macropores. Next, the internal surface is functionalized with mercaptopropyl trimethoxysilane (MPTMS). Subsequently, the micropillars are released by etching the back side of silicon wafers using a solution of tetramethylammonium hydroxide (TMAH). Finally, the external surface of the micropillars is chemically modified in a multi-step biofunctionalization with aminopropyl triethoxysilane (APTES), glutaraldehyde (GTA) and bovine serum albumin (BSA). The resulting structures were characterized by scanning electron microscopy and the surface reactions were confirmed by Fourier-transform infrared spectroscopy. The internal and external sides were photolabeled with tetramethyl rhodamine-5-maleimide and fluorescein isothiocyanate (FITC), respectively, and analyzed using fluorescence confocal microscopy. The peculiar three-dimensional (3D) geometry of the micropillars allows these double-active surfaces to be imaged at the same time. Results demonstrated the successful dual-side chemical modification and the feasibility of imaging both internal and external sides. Due to its remarkable architecture and chemical versatility, these micropillar arrays are a promising engineered platform for a range of applications such as biosensing, 3D cell culture and drug delivery.