The stability of a zirconium (Zr)-substituted face-centered cubic (FCC) yttrium (Y) hydride (Y1-xZrx hydride) phase was investigated experimentally and theoretically. Two possible sites for hydrogen atoms exist in the FCC structure, namely, T- and O-sites, where hydrogen is present at the center of the tetrahedron and the octahedron composed of Y and/or Zr metals. The P-C isotherms revealed that the hydrogen content per metal (H/M) with 33% Zr-substituted YH3-δ was 2.2-2.3, which was lower than the expected value calculated from the starting composition of YH3-33% ZrH2 (Y0.67Zr0.33H2.67, H/M = 2.67). Hydrogen at the O-site in Y1-xZrx hydride mainly reacted during hydrogen desorption/absorption. On the basis of theoretical analyses, the hydrogen atoms do not occupy the center of the octahedron, when at least two of the six vertices of the octahedron were composed of Zr. The O-sites, where more than two Zr atoms coordinate, nonlinearly increased with the Zr content, and when the Zr content was >50%, almost no hydrogen atoms occupy the O-sites. The theoretical discussion supported the experimental results, and the Zr substitution was confirmed to reduce the occupancy of H at the O-site in the FCC YH3 significantly.