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Abstract: The effective stress of marine sediments frequently shifts owing to natural or anthropogenic factors, and a broad spectrum of processes fundamentally require accounting for sediment responses to such changes. Marine sediments hosting natural gas hydrates have been regarded as a prospective energy reservoir, and depressurization-driven production efficiency hinges largely on the effective absolute permeability of hydrate-bearing strata. Yet, how this permeability evolves during depressurization remains unresolved, and whether pore-hosted hydrates impede or enhance it remains ambiguous. This study probes the permeability response of hydrate-bearing sands to cyclic loading through isotropic compression/swelling and water flow tests. Results reveal that methane hydrate presence curbs the void-ratio decline yet amplifies the effective-void-ratio reduction during isotropic loading. The effective absolute permeability of hydrate-bearing sands declines with rising hydrate saturation and increasing mean effective stress, and permeability stress sensitivity intensifies at higher hydrate saturations and lower mean effective stresses. The introduced model accurately predicts void-ratio changes during isotropic loading and unloading. Coefficients for strengthening, normal filling, and enhanced filling effects are introduced and quantified to disentangle the positive and negative influences of methane hydrate, with the negative filling effect exceeding the positive strengthening effect by one order of magnitude for quartz sands.