Amorphous mesoporous materials derived from synthetic saponite (Sap) by acid treatment have been used in catalysis for several decades. Uncovering the transformation process of Sap from layered to amorphous structure under acid attack is beneficial to optimize the structure of Sap-derived mesoporous materials, yet such transformation process remains unclear. Herein, a magnesium-Sap was synthesized by hydrothermal method and then treated with sulfuric acid. By studying the changes in phase composition, morphology, chemical state of elements and surface area of the synthetic Sap after acid attack, a specified transformation mechanism of synthetic Sap to amorphous silica is clarified. The experimental results indicate that after leaching of Mg and Al cations from the Mg/AlO6 octahedral sheets of Sap during acid attack, the retained SiO4 tetrahedral sheets of Sap were transformed into amorphous short-range ordered silica phases and nanoscrolls with pseudohexagonal side pores. The transformation process of synthetic Sap under acid attack can be divided into leaching of metal ions from octahedral sheets of Sap to form layered silica particles, splitting and crimping of surface nano-silica layers from the formed silica particles, and completely amorphous transformation. The distortion of SiO bonds in SiO4 tetrahedral sheets during acid attack might be the driving force for such transformation. This work provides specific transformation process of synthetic Sap under acid attack which is conductive to the controllable preparation of acid-treated Sap derivates, and has certain significance for understanding of structural transformation of clay minerals with MgO6 octahedral structure.