Striker Lafferty and captain Hughes both suffered their injuries in Friday's Group C defeat to Serbia, with the Rangers man taken off at half-time having experienced stiffness in his knee.
Fulham defender Hughes, meanwhile, bravely played the full 90 minutes despite dislocating his shoulder midway through the first period.
Heading home: Lafferty (right) has returned to Rangers
Nigel Worthington admitted after the match he had injury doubts but hoped at least one of the players would be available at Windsor Park.
Instead neither is with the side as they train in Belfast.
Millwall striker Josh McQuoid has been summoned to provide attacking cover in the absence of Lafferty and the suspended David Healy.
'Kyle will have to go back to Rangers for treatment and obviously David is out,' Worthington told the Belfast Telegraph.
'Aaron didn't travel to Belfast with us, instead he got a flight to London for a scan on his shoulder and it revealed some damage.
'Fulham are going to let it settle for a few days before seeing if the problem needs some further work, but his absence is, of course, a big blow for us.'
Explaining the decision to add McQuoid, who made his debut against Morocco last year, to an attacking pool that includes just Warren Feeney and Liam Boyce as established strikers, Worthington added: 'Josh is a good young player with plenty to offer us.
'He has a good turn of pace and is full of enthusiasm and drive and will be a welcome addition for what is now a very big game. He is also another young player in the squad and I really see that as the way forward for us.'
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Explore more:People: Kyle Lafferty, Warren Feeney, Nigel Worthington, David Healy Places: Belfast, London, Slovenia, Morocco, Northern Ireland