The blue phase, which emerges between cholesteric and isotropic phases within a threedimensional periodical superstructure, is of great significance in display and photonic applications. The crystalline orientation plays an important role in the macroscopic performance of the blue phase, where the single crystal shows higher uniformity over the polydomain and monodomain, resulting in higher Bragg reflection intensity, lower hysteresis, and lower driving voltage. However, currently reported methods of forming a single-crystal blue phase based on thermal controlling or e-beam lithography are quite time-consuming or expensive for large-scale fabrication, especially in the centimeter range, thus hindering the broad practical applications of single-crystal blue-phase-based photonic devices. Herein, a strategy to fabricate a large scale single crystalline blue-phase domain using holography lithography is proposed. Defect-free single-crystal domains both in blue phase I and blue phase II with a desired orientation of over 1 cm 2 are fabricated based on a nanopatterned grating with periodic homeotropic and degenerate parallel anchoring, with colors from red and green to blue. This holography lithography-assisted strategy for fabrication of a large-scale singlecrystal blue phase provides a time-saving and low-cost method for a defect-free single crystalline structure, leading to broad applications in liquid crystal displays, laser devices, adaptive optics elements, and electrooptical devices.