The game has been scheduled for 10.30am GMT (12.30pm local time) due to fears over fan violence.
Last May, Napoli fan Ciro Esposito was shot and killed by a hardline Roma 'ultra' supporter on the fringes of the Italian Cup final.
City officials have banned visiting Napoli fans from the game and ticket sales among the Roma supporters are not expected to soar either.
But the match itself is crucial to both sides' Champions League qualification hopes.
With Juventus boasting a 14-point lead over second-placed Roma, the Bianconeri look to already have a fourth consecutive scudetto sewn up.
But the race to join them in the Champions League next season is far from over, and faltering Roma are the target for several hopefuls, including Napoli.
A remarkable return of eight draws from a recent nine-game run effectively ended Roma's title hopes and left Rudi Garcia's men holding just a one-point lead over city rivals Lazio with 10 games remaining.
Sampdoria sit in fourth, four points further adrift, with Napoli in fifth a further point off the pace.
Roma finally got back to winning ways away to Cesena prior to the international break, but will be without injured striker Gervinho.
Roma forward Adem Ljajic says beating Napoli is important to keep Lazio at bay.
"Saturday's game counts a lot for both sides, but we want to go out and play our game and try to win," Ljajic said.
"Lazio are a top side and are having a great run at the moment, but for now we're in second and we'll do everything to stay there."
While victory has eluded Roma of late, Napoli have not exactly been blazing a trail, dropping five points behind Lazio after winning only one of their last six league games.
An eventual slip-up by Roma could see high-flying Lazio, who are away at Cagliari, move up to second place, adding spice to the existing bitter rivalry between the capital clubs.
"Finishing second (behind Juve but above Roma) would be like winning the title for us," Lazio captain Stefano Mauri told Sky Sport. "In the city, people are really starting to feel the rivalry and our fans are desperate for us to go ahead of Roma."
Fiorentina host Sampdoria in a clash that, while considered crucial for their respective European hopes, was already expected to serve up a cracking game between two attacking sides.
Vincenzo Montella's men have lost only once in their last 11 league games but welcome Sinisa Mihajlovic's team with doubts over the availability of winger Manuel Pasqual and defender Stefan Savic.
Sampdoria are looking for their fifth win on the trot and should be confident following a well-deserved home win over Inter Milan two weeks ago that left Mihajlovic purring.
"It was the best football we've played all season," said the Serbian.
AC Milan face a tough trip to Palermo as they chase a Europa League place, while city rivals Inter, a further point off the pace in 10th spot, host basement side Parma.
Juventus, who have lost only once this season, are in action late on Saturday when they host a tenacious Empoli side that is unbeaten in eight games.