Police allege four men armed with machetes forced their way into a house in Greenacre, western Sydney, in the early hours of Saturday morning.
A 23-year-old man confronted the men and was struck by a machete which severed his hand, Bankstown police superintendent Rodney Hart said.
"His father came out of the main bedroom and was also confronted by the offenders, who demanded cash," he said.
"They forced him back into the main bedroom where a safe was located, it was opened by the victim and a large sum of money has been stolen."
The alleged offenders then fled the scene in a dark-coloured SUV before emergency services arrived.
The man was treated at the scene before being taken to hospital where he is having surgery.
Police believe it was a targeted attack on the home due to a large amount of money from a business being held there.
The family is well known in the community and Supt Hart called for assistance to find the alleged offenders.
"This is a brutal, violent attack which is extremely traumatic for the family," he said.
"There is no indication that this is related to any organised crime.
"Somehow these people were aware that there may have been cash on the premises and that's what's been targeted, but unfortunately this has been a brutal home invasion where this young man will have received life-altering injuries."
Anyone with information has been urged to contact Crime Stoppers on 1800 333 000.
Meanwhile, in a separate incident, a man is in hospital and another is in custody following an alleged stabbing in Sydney's inner west.
Just after 10.30pm on Friday, emergency services were called to a unit in Newtown, after reports a 32-year-old man had been stabbed by a 54-year-old man who was known to him.
Paramedics treated the stabbed man before he was taken to hospital in a stable condition.
The older man was also treated for minor injuries before he was taken to Newtown police station.
The stabbing incidents come after a shocking home invasion earlier in the week in Torrington, a small town in northern NSW, which has left an elderly couple fighting for their lives.
In the early hours of Thursday, a 75-year-old man shot the alleged attacker in the abdomen after he and his wife suffered stab wounds during a break in.
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