The coupled flow deformation behavior in the porous media has drawn tremendous attention in various scientific and engineering fields. It is reported that the porous media will be compressed and relative permeability in porous media will be changed as the effective stress increases. However, previous studies provided contradictory evidence for the stress-dependent irreducible water saturation and stress-dependent relative permeability. Until now, appropriate stress-dependent relative permeability curve for two-phase flow through porous media remains unclear. The goal of this work was to theoretically and experimentally study the stress-dependent relative permeability. Laboratory sample flooding tests were conducted to measure two-phase relative permeability in porous media under changing effective stress, and a corresponding theoretical model of stress-dependent relative permeability was derived to interpret the experimental results. The predictions from the proposed analytical model exhibited similar variation trends as the experimental data, which verified the theoretical model. Though the results for the stress-dependent relative permeability from previous studies are different, or even opposite, our proposed model with different conditions can provide explanations to these different results. This work provides a comprehensive experimental and theoretical study of stress-dependent relative permeability in porous media, which is beneficial to accurate performance forecasts for the coupled flow deformation behavior in porous media.