Much attention has been paid to the biological effects of microwave irradiation. The hydration water surrounding a biomolecule is crucial in its biological reactions and functions. Therefore, it is important to know the response of hydration water to microwaves to understand their biological effects; however, the scarcity of studies about it often leads to speculations and debates about that effect. In this study, we have made real-time temperature measurements of reverse micellar solutions with their water droplet size from ∼2.3 to ∼9.5 nm using a waveguide system combined with a microwave generator at 2.45 GHz. The heat generated by water in reverse micelles has been observed to depend on their size. It is about 10 times larger than that of liquid water at their small sizes (<∼3.5 nm) and diminishes with further enlarging the size, approaching the water's value at their large sizes (∼10 nm). These results indicate that the heat generation behavior has an interfacial effect; specifically, the hydration water on the surfactant layer produces heat 10 times larger than bulk water. Moreover, the hydration number per surfactant molecule decreases in a core-shell model with increasing the reverse micelle size. These features are also reflected in the heat generation rate. Our findings may offer a new and fundamental perspective for studies on the biological effects of microwave irradiation.