Pressure reduction in liquids may result in vaporization and bubble formation—a process known as cavitation. It is commonly observed in hydraulic machinery, ship propellers and even in the context of medical therapy within the human body. Although cavitation may be beneficial for the removal of malign tissue, in many cases it is unwanted due to its ability to erode nearly any material in close contact. The current understanding is that the origins of heterogeneous cavitation are nucleation sites where stable gas cavities reside, for example, on contaminant particles, submerged surfaces or shell-stabilized microscopic bubbles^1,2. Here we present the discovery of an atomically smooth interface between two immiscible liquids acting as a nucleation site. The non-polar liquid has a higher gas solubility and, upon pressure reduction, it acts as a gas reservoir as gas accumulates at the interface. We describe experiments that reveal the formation of cavitation on non-polar droplets in contact with water, and elucidate the working mechanism that leads to the nucleation of gas pockets through simulations.