Asphaltene desorption from silica-coated quartz crystal surface, in the presence of a highly charged amphiphilic macromolecule (polyacryloyloxyethyl-N,N-dimethyl-N-benzylammonium bromide, denoted as PASBn), was investigated through a quartz crystal microbalance with dissipation, atomic force microcopy, and ultraviolet spectroscopy measurements. The results showed that asphaltenes were displaced by PASBn even at a low concentration of 0.5 g/L, mainly attributed to the electrostatic, polar, and hydrophobic interactions between asphaltenes and PASBn, as well as the electrostatic interactions between PASBn and binding sites of the solid surface. In order to understand the processes of asphaltene desorption and PASBn adsorption, the random sequential adsorption model was introduced. Unfortunately, this classical model was not consistent with the kinetic process of asphaltenes exposed to PASBn aqueous solution, due to the complex adsorption desorption processes, including the detachment of asphaltenes, subsequent transport of the detached ones to the bulk, and the adsorption of PASBn. Furthermore, a new kinetic model and a reasonable physical model were proposed to reveal the desorption mechanism of asphaltenes from the solid/liquid interface, providing a new way of improving heavy oil recovery.