ABSTRACT Stress sensitivity is an inevitable issue in the depletion exploitation of tight oil reservoirs, especially in the reformed multiscale region. Through a series of improved laboratory experiments, the stress sensitivity characteristics of multiscale media were thoroughly evaluated based on the primitive effective stress. Furthermore, based on the nonlinear seepage theory and equivalent seepage resistance method, a corresponding multiscale production prediction model of vertical wells in tight oil reservoirs with stress sensitivity established. The results showed that the decline in permeability of main fracture rock (12.86%) was more than twice that of the microfracture rock (5.25%), which was approximately four times that of the matrix rock (3.32%) in the selected pressure range. In addition, there was a fine power function relationship between permeability variation and effective stress in multiscale representative media. Compared with the actual daily production and cumulative production of the coring well, the production curve fitting of the proposed multiscale model was 91.25%, which was reliable to guide the development scheme design in the target block of tight oil reservoirs.