Abstract Palmitic acid, the main saturated fatty acid, is related with a wide range of metabolic disorders such as obesity, type 2 diabetes and heart disease. It is known that palmitic acid disturbs the expression of some important proteins for cell homeostasis such as SERCA and RGS2, however, the role of this lipid at the molecular level in these disorders is not completely elucidated. Thus, our aim was to determinate the effect of palmitic acid in a relevant cell process as it is cell migration and the participation of SERCA and RGS2 in this response. We found that palmitic acid reduces cell migration (determined by the Boyden chamber method) in an epithelial cell line (HEK293) and this effect is modulated by SERCA and RGS2 differential protein expression (measured by western blot). Also, overexpression of individual proteins, RGS2 and SERCA, produced a decrease and an increase on cell migration, respectively. Taken together, these data suggest that the expression of regulatory proteins is affected by high concentrations of saturated fatty acids and in consequence cell migration is diminished in epithelial cells.