X-ray radio-luminescence materials have potential application in radiotherapy (RT) and biomedical imaging. Considering that lutecium ions (Lu3+) with high atomic number (Z) have high X-ray attenuation coefficients, Ce3+-doped A-type Lu2SiO5@SiO2 (A-LSO:Ce3+@SiO2) core-shell nanospheres with size in the range of 200-250 nm were prepared through coprecipitation method. The growth mechanism of A-LSO:Ce3+@SiO2 core-shell nanospheres was investigated through determining the phase transition and morphology evolution by XRD, FT-IR, and TEM. The emission spectra, decay profile, and X-ray excited luminescence spectra (XEL) of the obtained samples were collected. The results show that a new type of lutecium silicate core-shell nanospheres A-LSO:Ce3+@SiO2 can be fabricated and exhibit efficient radio-luminescence under X-ray radiation, which has potential application in the diagnosis and therapy of cancer.