This study investigates energy harvesting by a deionized (DI) water droplet flow on an epitaxial graphene film on a SiC substrate. We obtain an epitaxial single-crystal graphene film by annealing a 4H-SiC substrate. Energy harvesting of the solution droplet flow on the graphene surface has been investigated by using NaCl or HCl solutions. This study validates the voltage generated from the DI water flow on the epitaxial graphene film. The maximum generated voltage was as high as 100 mV, which was a quite large value compared with the previous reports. Furthermore, we measure the dependence of flow direction on electrode configuration. The generated voltages are independent of the electrode configuration, indicating that the DI water flow direction is not influenced by the voltage generation for the single-crystal epitaxial graphene film. Based on these results, the origin of the voltage generation on the epitaxial graphene film is not only an outcome of the fluctuation of the electrical-double layer, resulting in the breaking of the uniform balance of the surface charges, but also other factors such as the charges in the DI water or frictional electrification. In addition, the buffer layer has no effect on the epitaxial graphene film on the SiC substrate.