A MOSFET with an isolation structure is provided. An N-type MOSFET includes a first N-type buried layer and a P-type epitaxial layer disposed in a P-type substrate. A P-type FET includes a second N-type buried layer and the P-type epitaxial layer disposed in the P-type substrate. The first, second N-type buried layers and the P-type epitaxial layer provide isolation between FETs. In addition, a plurality of separated P-type regions disposed in the P-type epitaxial layer further provides an isolation effect. A first gap exists between a first thick field oxide layer and a first P-type region, for raising a breakdown voltage of the N-type FET. A second gap exists between a second thick field oxide layer and a second N-well, for raising a breakdown voltage of the P-type FET.