A novel amine-functionalized ionic liquid-based periodic mesoporous organosilica (PMO-IL-NH₂) was prepared and characterized and its catalytic performance was investigated in the Knoevenagel reaction. PMO-IL-NH₂ was prepared by simultaneous co-condensation of 3-aminopropyltrimethoxysilane, an ionic liquid and tetramethoxysilane in the presence of a surfactant template under acidic conditions. The material was characterized by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The catalytic application of PMO-IL-NH₂ was then successfully carried out in the Knoevenagel condensation of a variety of different aldehydes with ethyl cyanoacetate under solvent-free conditions at room temperature, giving high to excellent yields of the corresponding products. The catalyst was also recovered and reused several times without a significant decrease in either activity or product selectivity. The TEM image and nitrogen sorption analysis of the recovered catalyst after the fifth reaction cycle confirmed its high stability and durability under the applied reaction conditions.