An ESD protection circuit suitable for applying in an integrated circuit with separated power domains is provided. The circuit includes a P-type MOSFET coupled between a first circuit in a first power domain and a second circuit in a second power domain. A source terminal of the P-type MOSFET is coupled to a connection node for connecting the first circuit and the second circuit. A gate terminal of the P-type MOSFET is coupled to a positive power line of the second power domain. A drain terminal of the P-type MOSFET is coupled to a negative power line of the second power domain. A body terminal of the P-type MOSFET is also coupled to the connection node.