Both sides are currently in the bottom three and Le Tissier reckons Saints will be in serious danger if they do not shackle Royals bruiser Jason Roberts.
He told The Sun: "Roberts played against us last season and gave our defenders serious trouble. He's a real handful.
"He isn't known as goalscorer but he got one against us - and we need to keep him quiet at the weekend.
"He could cause Southampton real damage."
Le Tissier insists St Mary's will be rocking on Saturday. He added: "The fans will be really up for it - it'll be a great game.
"That's what they love down there."