An in situ investigation of the epitaxial oxide layer formed on a thin specimen heated in a transmission electron microscope was carried out. Some dot-like grains about 10 nm in size were formed on the surface of a relatively thin area. The dot-like grains are monoclinic zirconium oxide and have an orientation relationship of (001)m//(01¯11)α-Zr, (001)m//(11¯01)α-Zr, with the α-Zr matrix. Some long strip-like grains, probably a new kind of zirconium suboxide, were formed on the surface of a relatively thick area. The strip-like grains have a bcc structure with a lattice parameter a=0.66 nm and have an orientation relationship of (110)_bcc//(10110)_α−Zr, [1110]_bcc//[0001]_α−Zr with the α-Zr matrix. The relationship between the thickness of oxide layers and the grain orientations of the α-Zr matrix was studied with coarse-grained Zircaloy-4 specimens through autoclave corrosion tests at 500 and 400°C in superheated steam, and at 360°C in both lithiated and deionized water for long time exposure. The results show that the anisotropic growth of oxide layers on the grain surface with different orientations is considerable. However, the relationship between the thickness of oxide layers and the grain orientations of the α-Zr matrix varies with corrosion temperature and water chemistry. The largest variation of oxide thickness developed during corrosion tests at 500°C. The thickest oxide layers were formed on those grains whose surface orientations were distributed around the planes from (011¯0) to (1¯21¯0). The thicker oxide layers on these grains were further developed into nodular corrosion. When the specimens were corroded at 360°C in lithiated water, the thickest oxide layers formed on those grains, whose surface orientations tilted from 15 to 30° away from the (0001) plane. When the specimens were corroded at 400°C in superheated steam and at 360°C in deionized water, the difference between the thickness of oxide layers on different grain surfaces was less prominent.