After becoming established in the Southampton defence, Powell picked up a three-game suspension against Reading at the end of September and has not featured since, having being replaced by Michael Svensson.
Svensson may be rested at St Mary's tonight as he paces himself on his return after 18 months out, and Powell is desperate to face the Eagles and re-establish himself in the first team.
Powell said: "I don't know if I will get a chance to play, but obviously I would love to be involved for what is a really tasty fixture. I had some good times there and I still have a lot of friends at the club and keep in touch with a few of the players so I would love to figure in this one."
The teams are separated by goal difference, with Palace one place higher, but Southampton have yet to be beaten at home, although they have been frustratedhaving drawn five games at St Mary's. The Eagles, meanwhile, have suffered four stalemates on the road and only two defeats, so statistics indicate it will be a close call.
Both teams will be hoping for a result to keep in touch with Sheffield United and Reading, and Powell admits it is one neither side can afford to lose.
"It is a big game for us both," he added. "Palace are a good side and I am sure we will both be up there at the end of the season."
The hosts will be hoping that the highly-rated 16-year-old Theo Walcott can extend his run after scoring in three successive games. Manager Harry Redknapp will be without defender Chris Baird after the Northern Ireland international had knee surgery, but could recall Polish right-back Tomasz Hajto after he recovered from hamstring trouble.
The midfielder Matthew Oakley (hamstring) could also return after missing the 2-0 win over Stoke, although defender Martin Cranie is still struggling with a similar problem.
Palace have a doubt over their goalkeeper Gabor Kiraly after the 29-year-old sustained a chest injury on Saturday and had to be replaced by Julian Speroni.
Jobi McAnuff has recovered fully from an ankle injury, but might struggle to regain a starting spot as Michael Hughes has impressed on the left in his absence. Gary Borrowdale could be preferred to Danny Butterfield at right-back, but long-term casualties Andrew Johnson, Mikele Leigertwood, Danny Granville and Tony Popovic are all still out.
Derby and Coventry will be looking to utilise home advantage as they attempt to pull away from the drop zone when they host Ipswich and Stoke, respectively.