Western Sydney confirmed on Wednesday that the star forward will be sidelined for the next three months with a fracture suffered during their 1-0 victory at Allianz Stadium.
The 28-year-old was fouled by Sky Blues skipper Luke Brattan in the opening minutes on Saturday night and replaced in the 17th. It's a devastating blow for Borello, who has fought hard to earn back his spot in the national side after missing out on selection in last year's World Cup squad.
He scored in a runaway 7-0 win over Bangladesh and also against Ecuador in March when they went down 2-1.
Borrello was called up earlier this year following injuries to forwards Jason Cummings and Jamie Maclaren and with just seven weeks remaining until the Asian Cup in Qatar, Socceroos coach Graham Arnold will need to look for a replacement.
It's the latest headache for Arnold, who will be looking to finalise his squad in the coming weeks. Scottish-based wing-back Ryan Strain suffered a groin injury during the Palestine qualifier, which may see him sidelined for weeks.
Melbourne City winger Matthew Leckie has been out since September with a knee injury and there has been no word when he is set to return, while Middlesbrough midfielder Riley McGree is still out with a foot injury and missed friendlies against England and New Zealand in October.
Borello's injury makes way for possible selection for young forwards Kusini Yengi and Samuel Silvera, who both debuted earlier this year.
The Socceroos' Asian Cup Group B campaign kicks off on Jan. 13 against India.