12-Tungstophosphoric acid supported on nanosilica (TPA/SiO2) was employed as a catalyst for the tertiary butylation of p-cresol using tertiary butanol as an alkylating agent. The TPA/SiO2 catalyst was synthesized using the wet impregnation method followed by steaming at 150 °C for 6 h. The catalysts were characterized by means of X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM) analysis. The surface acidity of the untreated and steamed catalysts was characterized via FTIR and DSC thermal analysis using pyridine as a probe molecule. The fresh and spent catalysts were characterized via TGA analysis. The catalytic activity studies showed that the steamed catalyst displayed higher activity, with a higher desired yield of 2-tert-butyl cresol (2-TBC) compared to the untreated catalyst, and that this activity was related to the presence of stronger Brønsted acid sites in the steamed catalyst. A detailed analysis of the TPA/SiO2 steamed catalyst was performed to study the effects of reactant time-on-stream, reactant feed rate, reaction temperature, and the molar ratio of tert-butanol to p-cresol. The optimum reaction temperature, tert-butanol/p-cresol molar ratio, feed rate, and time-on-stream were 413 K, a molar ratio of 2:1, 6 mL/min, and 2 h, respectively. The present study demonstrates that the TPA/SiO2 catalyst exhibits high activity in terms of % conversion and high % selectivity of 2-TBC under the optimized conditions. The characterization of fresh and spent catalysts confirmed the occurrence of coke deposition after the catalytic reaction. The catalyst was regenerated via heat treatment at 400 °C for 5 h. The regenerated catalyst was reused for subsequent runs for three cycles without showing a loss in its activity.