A (Lu,Y)2SiO5:Ce (LYSO) crystal, as a heavy inorganic scintillator, is currently in high demand for various applications in the fields of particle detection. However, its high refractive index (n = 1.83) gives restriction on the measurements of rare events or weak particle flow, where high energy resolution is urgently required for detectors based on the crystal. Utilizing the electron beam lithography technique and the ion beam lithography method, we have successfully prepared a 2.0 × 2.0 mm2 large area two-dimensional photonic crystal (PhC) structure on the LYSO crystal surface. Compared with the plain reference sample, the optical measurements show a 53% enhancement of light extraction for the LYSO nanostructured surface, and the resulted improvement of energy resolution (full width at half maximum) is measured to be 43.8% by gaussian fittings to the energy spectra excited by the 241Am α source. With the advantage of high-resolution patterning, high thermal stability, and firm stickiness on the substrate, the present prescription of the PhC fabrication is still favorable for some special fields (e.g., homeland security and space exploration) though the writing process is extremely time consuming and expensive to use.