Grotto murals are a very precious cultural heritage. However, preservation of them has been threatened by damage caused by soluble salts. An in-depth investigation of the mechanism of damage by soluble salts in murals is crucial for the prevention and treatment of this sort of damage. Both in-situ surveys and laboratory simulation work are needed to fully understand this damage. This study, which is based on preliminary work by the Dunhuang Academy, diagnoses of mural diseases and knowledge of traditional crafts, proposes a standard method for preparing mural samples and successfully simulates the process of migration, the profile of soluble salt distribution and the degree of damage caused. The different physical properties of samples can be measured conveniently, and the results of the simulation generally agreed with actual situation data from the Mogao Grottoes.