A zinc oxide (ZnO) single crystal was used as a substrate in the hydride vapor-phase epitaxy (HVPE) growth of GaN and the structural and optical properties of GaN layer were characterized by x- ray diffraction, transmission electron microscopy, secondary ion mass spectrometry, and photoluminescence (PL) analysis. Despite a good lattice match and an identical structure, ZnO is not an appropriate substrate for application of HVPE growth of GaN. Thick film could not be grown. The substrate reacted with process gases and Ga, being unstable at high temperatures. The crystallinity of ZnO substrate deteriorated seriously with growth time, and a thin alloy layer formed at the growth interface due to the reaction between ZnO and GaN. The PL from a GaN layer demonstrated the impurity contamination during growth possibly due to the out-diffusion from the substrate.