Rovers manager Gary Brabin says he is looking forward to going back to the Merseyrail Community Stadium this afternoon with his Tranmere side.
Brabin has had three different spells at Southport and he's expecting a warm welcome from his former employers.
He told Tranmere Player: "It's always nice to go back to a former club. It's a good club and I sincerely hope that after Saturday they get back on track.
"We're expecting another tough game. There are different types of challenges for us but we need to overcome everything that comes against us."
Rovers go into Saturday's game with a 100% record so far with five wins from five matches at the start of the season.
The successful start to the season means Tranmere are top of the National League while Southport, who have lost four of their opening games, are third from bottom.
Ahead of the weekend's local derby, Brabin says that they don't need to make special preparations ahead of the game as many opposition teams make a game against Rovers feel like a derby.
He added: "Every game we play seems to be like a derby game because the opposition are raising their game against us and Saturday is not going to be any different.
"We have to be 100% focused in every game and if we perform at our maximum level, we're always confident that we'll come out on top."
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