West Hams last home game, a 3-0 defeat by Burnley, was marred by pitch invasions and protests against owners David Sullivan and David Gold.
The Hammers are set to implement "heightened" security measures this weekend in a bid to avoid similar troubles.
West Ham have lost four of their last five Premier League matches and are 17th in the table, two points above Southampton, who occupy the final spot in the relegation zone.
Mark Hughes will be taking charge of his first league match as Southampton manager, having started with an FA Cup quarter-final win over Wigan.
"Its a key game for both sides," he said. "West Ham have their own problems to deal with, it seems, with their home games so we have got to take the opportunity, if it presents itself, to be able to exert pressure on them and maybe affect the atmosphere in the ground and what seemed to occur against Burnley.
"Weve got to affect the confidence of their group. Clearly there is some anxiety surrounding the club at the moment.
"Thats a negative and it certainly affected them in the last game, going by what some of their players talked about afterwards."
Charlie Austin is in contention for Southampton after recovering from the hamstring injury which had kept him out since Christmas.
Captain Steven Davis is also close to returning from his hamstring problem.
Edimilson Fernandes is available again for West Ham after four months out with an ankle injury. Arthur Masuaku is also back after completing a six-match ban.
However, Manuel Lanzini is a doubt with a knee injury and James Collins faces a late fitness test.
