The invention provides an isolation structure and a manufacturing method thereof for a high-voltage device in a high-voltage BCD process, the isolation structure comprising: a semiconductor substrate having a first type of doping; an epitaxial layer having a second type of doping over the semiconductor substrate, wherein the first type of doping is opposite to the second type of doping; an isolation region having the first type of doping, wherein the isolation region extends through the epitaxial layer into the semiconductor substrate, and wherein the isolation region has a doping concentration on the same order as a doping concentration of the epitaxial layer; a field oxide layer over the isolation region. This invention effectively isolates the epitaxial island where the BCD high-voltage device is located, thereby increasing the breakdown voltage of the high-voltage device in the BCD process. Further, with a minimum thickness of the field oxide layer, the parasitical threshold voltage between the aluminum wiring and the silicon surface of the high-voltage device can be higher than 1200V, thereby improving the planarization of oxide layer steps on the silicon surface in the whole high-voltage BCD process, and enhancing the reliability of the product.