Resulting　from　the　bedding　structure　of　turbidite　reservoir,　permeability　anisotropy　is　an　essential　parameter　for　natural　gas　hydrate　(NGH)　exploitation.　Fundamentally,　the　evolution　of　permeability　anisotropy　under　increasing　effective　stress　are　investigated　in　this　study.　Taking　the　turbidite　sediments　in　northern　Cascadia　as　an　example,　a　series　of　experimental　tests　and　co-simulations　of　discrete　element　method　(DEM)　and　computational　fluid　dynamics　method　(CFD)　are　conducted.　For　layered　turbidite　sediments,　an　interlayer　mixed　zone　will　be　formed　in　the　interface　between　fine-grained　layer　and　coarse-grained　layer　after　loading.　Fine　particles　will　migrate　to　the　coarse　layer,　blocking　the　horizontal　preponderance　flow　paths　and　further　reduce　the　permeability　anisotropy.　Moreover,　the　development　of　interlayer　mixed　zone　mainly　occurs　in　initial　compaction　stage　and　slows　down　in　higher　stress　level,　for　which　the　permeability　anisotropy　shows　a　staged　reduction　with　increasing　effective　stress.　Considering　the　effect　of　interlayer　mixed　zone,　a　predictive　model　of　permeability　anisotropy　is　proposed　and　verified　by　the　experimental　results,　which　has　higher　accuracy　than　traditional　＂layered　cake＂　model.　The　finding　of　this　research　also　confirms　the　mixing　effect　in　deep　sediments,　which　may　affect　the　geological　history　records　in　target　sedimentary　sequence.