Lutetium–yttrium-based scintillators, such as LYSO:Ce, have a high effective atomic number, are non-hygroscopic, fast emitting materials, and promising candidates for use in positron emission imagers. The present study investigates the light emission characteristics of (Lu, Y) 2SiO 5:Ce (LYSO:Ce) single-crystal scintillator under X-ray imaging conditions. Also, the parameters related to the luminescence emission spectrum and emission efficiency were studied using experimental methods. Various X-ray tube voltages currently employed in X-ray imaging techniques were used. Measurements were performed using an experimental set-up based on a photomultiplier coupled to an integration sphere. In addition, the emission spectrum under UV and X-ray excitation was measured using an optical grating monochromator to determine the spectral compatibility of optical photon detectors incorporated in medical imaging systems. The absolute efficiency of LYSO:Ce was found to increase with increasing X-ray tube voltage (from 2.2 EU at 22 kVp to 22.4 EU at 140 kVp), while its spectrum, peaking at about 430 nm, was found compatible with most optical detectors (photodiodes, photocathodes, charge coupled devices, etc.). The matching factor was estimated to range from 0.76 to 0.92 (for a silicon photodiode and for a GaAsP photocathode, respectively).