The game will be key for both teams in the battle to avoid relegation as it is only the goal difference that keeps Swansea in the relegation zone and Southampton just above.
Merson expects Swansea to be able to win the game against a Southampton side, who are playing well at the moment.
Merson predicts a 2-1 win to Swansea.
Merson told Sky Sports: “This is a cup final and as big as a Championship play-off final game – whoever wins, you would have to say is safe. Huddersfield will be sweating on Swansea winning this game as they have Stoke at home in their final game, while Southampton have Man City at home.
“Swansea have gone off the boil a bit though and they have tried to stick a few times – when you get these free swings, you are better off just going for it and gambling, instead of just playing to nick a draw.
“But at the end of the day, Swansea could win this game and stay up because of their goal difference, with them having not been smashed by other teams, so it is a bit of a catch-22.
“The game they will be kicking themselves about is Everton at home, which they dominated and they were by far the better team.
“If Southampton draw, they are out of it, but Swansea have two home games now. However, Swansea are good at home and have decent players, and I think Southampton have to win – they will not want to go into the final match against one of the greatest Premier League teams of all time needing to win.
“Southampton are playing well at the moment, they were good against Bournemouth, even though they were hanging on a bit at the end, and then they were unlucky against Everton.
“However, I am going to go for Swansea to win – I am going to forget their last few results, which were hard fixtures, and say they will win at home. And if it is 1-1 with 20 minutes to go, I do not see all-out attack from Swansea as I think they will take their chance on beating Stoke at home.”