Two-dimensional　(2D)　metal-halide　perovskites　have　shown　broad　application　prospects　in　the　field　of　optoelectronic　detection.　The　presence　of　the　natural　quantum-well　structure　results　in　strong　anisotropy　of　physical　properties,　while　studies　on　anisotropic　X-ray　responses　remain　insufficient.　Here,　we　present　an　intriguing　anisotropy　of　X-ray-responsive　behaviors　in　a　2D　halide　perovskite,　(t-ACH)2(DMA)Pb2Br7　(1,　where　t-ACH　is　trans-4-(aminomethyl)cyclohexanecarboxylate　and　DMA　is　dimethylamine),　in　which　the　secondary　amine　DMA+　cation　with　a　large　ionic　radius　locates　inside　the　perovskite　cage　to　form　inorganic　frameworks.　The　alternative　alignment　of　inorganic　slabs　and　organic　bilayers　creates　a　typical　quantum-well　architecture,　which　accounts　for　the　generation　of　photoelectronic　anisotropy.　High-quality　crystals　of　1　exhibit　notable　semiconducting　properties　with　a　large　μτ　product　(1.9　×　10-4　cm2　V-1).　Intriguingly,　1　has　better　X-ray　detection　sensitivity　(∼569.9　μC　Gyair-1　cm-2)　along　the　in-plane　direction,　which　is　attributed　to　its　excellent　charge　carrier　transport　performance　in　this　direction.　Conversely,　the　higher　resistance　stemming　from　the　organic　barrier　results　in　a　lower　detection　limit　along　the　out-of-plane　direction　(∼78.1　nGyair　s-1),　much　lower　than　the　medical　diagnostic　criteria　(∼5.5　μGyair　s-1).　This　work　might　open　up　new　possibilities　for　the　creative　use　of　hybrid　perovskites　in　direct　X-ray　detection.　©　2024　American　Chemical　Society.