The self-healing behavior of mudstone is an important topic, which has to be addressed in site assessment and stability analysis for the nuclear waste repository. With a high-level radioactive waste repository in mudstone as background, the laboratory experiments and field tests are performed, and the distribution model and self-healing model of permeability are developed with introducing a decaying exponential function. Based the long-term field monitoring data of excavation-disturbed zones, a hydromechanical (HM) coupling model, which can describe construction and excavation processes, is developed and implemented into a finite element code for the optimization analysis of the permeability coefficient, with combining a new exact penalty function and the Nelder-Mead algorithm. The permeability coefficients of the excavation-disturbed zone around a waste repository are studied using the proposed procedure. The results show that the permeability coefficients from both the inversion analysis and the measurements have the same magnitude of 10-12 m/s, and the calculated pore pressures are also very close to the measured data. The vertical permeability coefficient is disturbed by excavation more significantly compared to the horizontal permeability coefficient with regard to both the intensity and the extent, and indeed the magnitude of the vertical permeability coefficient is increased by 2 orders, while the disturbed area is about 25 m. The self-healing time is about 5 years.