Manager Michael O'Neill revealed on Wednesday that the duo were struggling with respective groin and knee problems.
Both players were expected to start against Portugal at Windsor Park on Friday night - with Hughes at right-back and McGivern deputising for the suspended Daniel Lafferty at left-back.
Craig Cathcart is already absent due to a knee injury and O'Neill has summoned Chris Baird and Rory McArdle as cover.
Baird is a vastly experienced player at international level and can play in a number of positions, but had not initially been considered for the double header as he is currently without a club.
The former Fulham man has been training with west London rivals Queens Park Rangers since pre-season but has yet to agree terms and has not played competitively this term.
Meanwhile, Bradford centre-back McArdle offers additional cover for Jonny Evans and Gareth McAuley.