SnO2 films with a thickness around 150 nm were deposited on the (111) surface of a SrTiO3 single crystal substrate by laser molecular beam epitaxy technique in a temperature range 600–750 °C and oxygen pressure from 10-3 to 1 Pa, respectively. The growth behavior was in situ monitored by reflection high-energy electron diffraction, and the epitaxial relations were further investigated by ex situ x-ray diffraction measurement in different geometries. All the films were confirmed to be highly (200) oriented showing good crystalline quality, despite the large lattice mismatch between SnO2 and SrTiO3. Based on the crystallographic model and structure analysis, six equivalent directions in the SrTiO3 (111) surface for the nucleation of SnO2 were discovered, which confirmed the existence of sixfold symmetrical domains in the SnO2 epilayer. Additionally, the optical dielectric function of the SnO2/SrTiO3 epitaxial film was simulated by the Tauc–Lorentz–Drude model in the UV-vis-NIR region.