High-pressure behaviors of wurtzite CdS and CdS:Eu3+ nanoparticles (8-10 nm) were investigated by synchrotron radiation X-ray diffraction, Raman spectroscopy, and photoluminescence under high pressure at ambient temperature. The doping of Eu ions increases the phase transition pressure from wurtzite structure to rocksalt structure (CdS = 4.76 GPa and CdS:Eu = 5.22 GPa) and so does the bulk modulus (B0) of the initial and high pressure phases. This phenomenon can be attributed to the great impact on tensile strain along the c-axis of CdS nanoparticles, which is identified by the relationship of lattice contraction and the pressure obtained from Raman 1LO. The phase transitions of all samples are partly reversible. The Eu3+ ions luminescence from 5D0 → 7FJ (J = 1, 2) transition in CdS:Eu nanoparticles emerges obviously and changes during the phase transformation, which indicate the variation of the local symmetry of the Eu3+ ions. The new peak of 5D0 → 7F3 emerges at 7.26 GPa, persisting until the end of the whole experiment. The obtained CdS nanoparticles will hold promising potential in the fabrication of effective biological sensors and photodetectors for practical application under high pressure.