Abstract: Supercritical carbon dioxide drying has been previously explored as an alternative to other techniques (e.g. air drying), which can retain the products original (micro) structure. It has been widely used in the production of inorganic and organic aerogels, for which preservation of the porous network during drying is essential to protect function. Drying by supercritical carbon dioxide just begins in the utilization of food processing. In order to probe into the mechanism of tilapia fillet drying by supercritical carbon dioxide, the conservation law of mass based on differential drying beds was used to establish the mass-transfer mathematic model of tilapia fillet drying by supercritical carbon dioxide. The model was simulated by software. It was analyzed that the content (mass fraction) of solute in supercritical carbon dioxide and in tilapia fillet changed with drying time and height of drying chamber. The mass-transfer model of solute in the process of drying by supercritical carbon dioxide was revealed. The results show that convective diffusion of solute was primary and axial diffusion was minor during the drying process of tilapia fillet by supercritical carbon dioxide. The results of numerical simulation with the experiment values were in good agreement (R2=0.97) and the absolute value of the relative deviation was less than 10%, which showed that the mass-transfer mathematic model could well simulate the process of tilapia fillet drying by supercritical carbon dioxide. The results can provide some helpful information for the industrial process control of tilapia fillet drying by supercritical CO2.