The exploitation of natural gas hydrates is in essence the process of hydrate dissociation from the solid phase into the gas and liquid phases, which is a complex problem involving phase transition and gas-water multi-phase flow. Permeability is a useful parameter for characterizing the flow capacity of sediments, and the pore-structure changes caused by hydrate dissociation make this parameter characterized by spatial and temporal evolution. Clayey silt sediments form the hydrate accumulation reservoir in the South China Sea, whose lithological characteristics (shallow buried deep, poor permeability, and low cementation) are unfavorable to fluid flow, leading to difficulties in the production prediction of clayey silt hydrate-bearing sediments. In this paper, the mutual feed-back mechanism between pore-structure and permeability during hydrate dissociation was clarified using the lattice Boltzmann model method. Core-scale seepage experiments were carried out to validate the dynamic evolution of permeability relationship. The permeability calculation module of Tough+Hydrate code was developed to quantitatively describe the evolution of this relationship, and the first hydrate production test in the Shenhu area was evaluated to validate the applicability of pore- and core-scale study at the site scale. This study clarifies the dynamic evolution mechanism of permeability during hydrate dissociation, and establishes a permeability evolution model in a S-shape suitable for clayey silt hydrate-bearing sediments.