The invention discloses a DC power supply fault quick isolation device for a transformer substation. The isolation device is serially connected between a DC power supply and each DC feed-out branch; the isolation device is between each DC feed-out branch and the DC power supply; an input end of the isolation device is connected with the DC power supply, the output end of the isolation device is connected with the DC load; the isolation device comprises a single chip microcomputer control circuit, a driving circuit, an IGBT module, an electric and electronic circuit breaker, a ground fault detection circuit and an isolation diode; a control signal output end of the single chip microcomputer control circuit is connected with control signal input ends of the IGBT module and the electric and electronic circuit breaker after being isolated and amplified through driving circuits; when the device is worked in the DC normal working mode, the single chip microcomputer turns off a PWM driving signal of the electric and electronic circuit breaker and directly supplies power for a DC load through the IGBT module; when the device is located in a DC fault working mode, the single chip microcomputer control circuit turns off a driving signal of the IGBT module and supplies power for the DC load through the electric and electronic circuit breaker.