The Scots go into the match with a two-point cushion over their hosts following their 1-0 Group D victory at Celtic Park last November.
A win for the visitors would all but end Martin O’Neill’s side’s chances of reaching the finals in France next summer but McGhee admits he is braced for a tough match against a side on a revenge mission.
McGhee, who is part of manager Gordon Strachan’s backroom staff, said: “You cannot build this match up enough in the scheme of what we have experienced as coaches. Coming to the job this is the biggest game we’ve had.
“Then the next one after that will become the biggest game and the next one after that will be even bigger.
“We recognise the importance of this game to everyone and we will be going there to try and win the game, although Ireland will be sitting saying the same thing.
“They were a little bit hurt by the result at Celtic Park and no doubt they will be looking for revenge and to keep themselves in the section. So I think it will be a tight game.”
And McGhee believes the arrival of the Republic’s talisman Robbie Keane will ensure his backline are kept on their toes at the Aviva Stadium, live on Sky Sports.
The former Tottenham and Liverpool striker has flown into the Irish capital after missing the goalless draw with England last weekend while on duty with his club LA Galaxy.
And McGhee is convinced the 34-year-old, who both he and Strachan had in their charge while managing Wolves and Coventry respectively, will have an impact from the start or coming off the bench.
“Robbie Keane can score goals anywhere and at any level,” added the former Aberdeen and Celtic striker. “He has proven that and he is still a top-class international player and if he is not in the team then I will be delighted.
“However, I will still be looking at the bench for the minute he comes on because he remains a threat, there is no doubt about it”