The Manchester United star scored two late goals to seal a 2-1 comeback win for Fernando Santos' side in the reverse fixture back in September.
Ireland are only playing for pride in front of their home fans having already been eliminated from qualification.
Stephen Kenny's men picked up only five points from their six games - winning just once against Azerbaijan during the last international break.
Ireland v Portugal: Date and kick-off time
The match will take place on Thursday 11 November, 2021 and will kick off at 7:45pm UK time.
It is being held at the The Dublin 4 venue in Ireland's capital city.
These two last met back in September where a John Egan header put Ireland on course for a famous win before Ronaldo struck late twice.
The Boys in Green are undefeated in four games since that loss while Portugal are currently one point behind Group A leaders Serbia with a game in hand.
Ireland v Portugal: How to follow
The game is being broadcast on Sky Sports Premier League from 7:30pm.
Sky Sports customers can live stream this via the app using their mobile, tablet or computer devices.
If not, you can purchase a Sky Sports Day Pass from NowTV for £9.99.
Ireland v Portugal: Team news
The hosts were forced into a late squad change with Callum O'Dowda replacing Cardiff City forward James Collins due to injury.
Brighton star Aaron Connolly was not selected but Jayson Molumby and Alan Browne are both available after serving their suspensions.
For Portugal, Bernardo Silva has been ruled out this evening after picking up an injury in Manchester City's 2-0 win over rivals United last Saturday.
He joins Portuguese trio Anthony Lopes, Rafa Silva and Joao Mario in playing no part in November's fixtures due to injury.
Nuno Medes is suspended meaning Joao Cancelo could continue at left-back with Diogo Dalot set to earn a start on the right hand side of defence.
Ireland v Portugal: What has been said?
Santos: "The most important game is against Ireland. We'll put in a strong team.
"It will be a tough game, they proved in Portugal that they are a competitive team. They are backed by the public, they never leave the game, they never give in.
"They fight a lot and they know how to play, they showed it here. They try to try to play with an organised attack.
"After 15, 20 minutes we could have been winning 2-0 [in Portugal]. We had a penalty and a shot hit the post.
"The important thing to take away from that game is the period between shooting at the post and the end of the first half.
"We allowed a more broken game, attack and counterattack, which appeals more to Ireland and did not help our team. In the second half the team reacted well, and no longer allowed Ireland that ability to create so many problems."