The results of laboratory studies to determine the effect of effective stress on the permeability of sandstone are presented. During the test, the samples were subjected to a stepwise increase or decrease of the effective stress (at a constant pore pressure) in a specified step. The values of rock permeability at different values of effective stress were determined, and the influence of the grain size of the reservoir rock matrix on the character of the change in the sandstone permeability coefficient was also established. During the test, a decrease in permeability was observed with an increase in effective stress. It was found that as a result of gradual loading/unloading of the sandstone sample, the original permeability values were not restored, which indicates the beginning of the formation of residual strains in the rock. This effect should be taken into account when modeling field development because in the process of reserves extraction the effective stress acting on the reservoir rock skeleton changes, which results in a significant chang in rock permeability. The results of laboratory studies showed that the deviation of permeability in medium-grained sandstones relative to the initial value was greater than in medium- and fine-grained sandstones. The pressure sensitivity coefficient and constant of material, which are used in empirical relationships between permeability and effective stress, were numerically estimated. At the same time, the constant of material showed no such convergence, which indicates that the values of this parameter are individual for each rock.