and then generate a high-energy photon through radiation transitions from the excited state. Compared with single photon excited luminescence, MPE luminescence has the advantages of stronger spatial confinement, longer penetration depth, smaller biological damage, and less Rayleigh scattering, so the high-order MPE luminescence materials have great potential applications in bioimaging, 3D optical data storage, sensing, and so on, but basically have not been fulfilled yet, [1][2][3][4][5] mainly because of the big challenge and difficulty to realize high-order MPE luminescence. Even for those materials exhibiting such MPE luminescence, the five-photon excited luminescence phenomena can be only observed in the dispersed solutions of either organic chromophore molecules or core-shell halide perovskite semiconductor nanocrystals (MAPbBr 3 /(OA) 2 PbBr 4 ) in order to diminish the aggregation-caused quenching (ACQ) while still with quite low multiphoton action cross-sections (MPACs), or have poor stability without any encapsulation approaches (The MPAC (ησ n ) is the product of photoluminescence quantum yield (PLQY, η) and multiphoton absorption cross-section (σ n ), the parameter to evaluate the multiphoton excited luminescence brightness). [6,7] The deficiency of bulky high-order MPE luminescence solid single crystals with low excitation threshold have further limited the exploration and implementation of such MPE materials into miniaturization and device, and thus their practical applications.Some porous materials such as mesoporous silica and porous alumina have been utilized to confine dye molecules and perovskite nanoparticles and thus to diminish the ACQ and to develop the solid-state luminescence. [4,[8][9][10][11] The emergence of a new type of porous materials, metal-organic frameworks (MOFs), has provided the significant promise to provide much better confinement for the potentially luminescent dye molecules and perovskite nanoparticles because of their more tunable pores/cages and specific sites to introduce strong recognitions. Indeed, we have recently realized a three-photon excited emissive material ZJU-68⊃DMASM through an exact match of a dye molecule with the pores of the metal-organic framework although high-order MPE luminescence solid single The development of the photostable higher-order multiphoton-excited (MPE) upconversion single microcrystalline material is fundamentally and technologically important, but very challenging. Here, up to five-photon excited luminescence in a host-guest metal-organic framework (MOF) and perovskite quantum dot (QD) hybrid single crystal ZJU-28⊃MAPbBr 3 is shown via an in situ growth approach. Such a MOF strategy not only results in a high QD loading concentration, but also significantly diminishes the aggregationcaused quenching (ACQ) effect, provides effective surface passivation, and greatly reduces the contact of the QDs with the external bad atmosphere due to the confinement effect and protection of the framework. These advantages make the resulting ZJU-28⊃MAPb...