This investigation focused on the study of formation mechanism for highly mesoporous ZSM-5 under the introduction of tetrapropylammonium hydroxide (TPAOH) during NaOH treatment. Determined based on N-2 sorption, transmission electron spectroscopy, scanning electron spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, inductively coupled plasma atomic emission spectroscopy, and Si-29 magic-angle spinning nuclear magnetic resonance characterizations, increased mesoporosity, crystallinity, and surface integrity for the desilicated ZSM-5 were found after TPAOH introduction. This protective effect of tetrapropylammonium (TPA(+)) on desilication was reflected by increased surface SiO2/Al2O3 ratios with increased concentrations of TPA(+). TPA(+) was first confirmed to be mainly adsorbed on the Si(4Si, 0Al) sites to provide a protective effect. Na+ played an indispensable role in the induced desilication during alkali treatment. The co-effect of protective desilication from TPA(+) and preferential desilication near Na+ on the surface accounts for the formation of ZSM-5 with high mesoporosity. Contributing to larger external surfaces, the TPAOH-aided desilicated sample possessed a longer methanol-to-hydrocarbons lifetime of 102 h, twice that of ZSM-5 treated by traditional NaOH treatment.