A killer is on the run after a father of two was fatally shot in the chest at his home in the suburb of MacGregor in Brisbane's south.

The man, aged 56, was taken to Princess Alexandra Hospital on Monday night after his wife dialled triple-0 about 11.40pm to say her husband had been shot.

However, he was later pronounced dead.

Police searched Delfin Drive, MacGregor for hours in the dark after the shooting, but could find no trace of the shooter who remains at large.

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Family members were at home at the time the man was shot by an assailant police say he didn't know.

Family friend Jimmy Huang told the Courier Mail he heard a loud gunshot followed by a five-second scream he believed was the "last breaths of the guy".

"It was not a normal scream from the guy. It was crying out," Huang said.

"It is (a shock). Normally you'd think MacGregor is a pretty safe place," he said.

Huang described the victim's family as "nice people", saying the victim and his wife were both doctors, with two daughters and a pair of grandparents all living at the home.

"I don't know what the hell happened," he said.

According to Nine Newspapers, the victim worked as a doctor in Brisbane's Chinese community on the city's south side. His wife is also a doctor and his children are studying medicine.