Sulfated titania nanoparticles (SO42-/TiO2 NPs) were synthesized using titanium tetraisopropoxide (TTIP) by the sol-gel method. The structure and morphology of the prepared nanocatalyst was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) and Brunauer–Emmett–Teller (BET) methods as well as Fourier transform infrared (FT-IR) and energy dispersive X-ray (EDX) spectroscopy. The obtained nanoparticles were used as an efficient, reusable and environmentally friendly catalyst for the synthesis of polyhydroquinoline (PHQ) derivatives via a one-pot multicomponent reaction of various aldehydes, ammonium acetate and 1,3-dicarbonyl compounds under reflux conditions. The desired Hantzsch esters were obtained in good to excellent yields and short reaction times. The SO42- /TiO2 NPs could be recycled at least three times without significant loss of their catalytic activity.