Manager Michael O'Neill revealed on Wednesday that the defensive pair were struggling with respective groin and knee injuries and his worst fears were confirmed after further assessment.
Had they been fit, both 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.
With Craig Cathcart already missing with a knee problem of his own, 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 due to being unattached.
He has been training with QPR since his release by Fulham at the end of last season but has yet to agree terms and has not played competitively this term.
Bradford centre-back McArdle, meanwhile, offers additional cover for Jonny Evans and Gareth McAuley.
Source: PA
Source: PA