Pochettino spent 18 months at St Mary's Stadium, guiding the club to 14th and eighth-placed finishes in the Premier League, before moving to White Hart Lane at the end of last season.
The Argentinian was charged with returning Spurs to the top four, but an inconsistent campaign sees them lie sixth in the table, seven points adrift of a UEFA Champions League qualifying berth.
"This season realistically it is very difficult to reach the top four," Pochettino conceded.
"We need to try. We have five games ahead, but at the same time I don't want to lie. It is not easy to reach the top four, realistically."
Midfielder Nabil Bentaleb made his Premier League debut in last season's corresponding fixture, which Spurs won 3-2, and the Algeria international knows his side are in for a stern test on the south coast.
"This is a big match and we have to be up for the fight," he told the club's official website. "We know what to expect from them and they will know what to expect from us.
"We have to be focused, strong and I'm sure it will be a good game. Hopefully we'll come back with the points.
"They've had a really good season. They are tough to play against, but we relish these challenges. As a footballer, you want to play in these matches and play with that pressure."
Tottenham defeated Newcastle United 3-1 last time out, which allowed them to climb one point above Southampton, who went down 2-1 at Stoke City.
Should Arsenal defeat Aston Villa in the FA Cup final next month, seventh place would seal a UEFA Europa League spot, but Southampton manager Ronald Koeman does not want to rely on others to secure European action next season.
"We know every game is important and okay, if Arsenal win the FA Cup, the seventh place is also the last European qualifying place to play the qualification round," he said.
"And the distance between the eighth [Swansea City] behind us is nine points. That seems to be enough, but we try to finish in the highest position in the table."
Southampton fans are planning a 'Ronald Koeman Day' on Saturday, with many preparing to wear the Dutch national colours of orange to support their manager.
"I heard something about that and I think it's nice because it's a nice appreciation of the fans about my job," he added.
"I know the connection between the manager and the fans is on a very good level and I'd like to keep that. And to keep that we have to win games."
Koeman confirmed on Thursday that Filip Djuricic (ankle) is still out, while Victor Wanyama is suspended, but Toby Alderweireld should be fit following a shoulder injury sustained at Stoke.
For Spurs, Hugo Lloris (knee) and Danny Rose (hamstring) are doubts, while Kyle Walker (foot) will be out for around four weeks.
