The Reds will face Carlo Ancelotti’s side for a second successive campaign and if last year was anything to go by, the trip to the San Paolo will not be easy.
Jurgen Klopp’s side were beaten 1-0 by a 90th minute strike from Lorenzo Insigne in a blow to their knockout qualification hopes.
But there is good news for Liverpool this time around, with the Italian international being a doubt for Tuesday’s contest.
According to Football Italia, the star has been training alone ahead of the clash.
Insigne is thought to have picked up the minor injury during the thrilling 4-3 defeat to Juventus before the international break.
He was forced to withdraw from the Azzurri’s Euro 2020 qualifiers with Armenia and Finland.
Insigne was also on target when Napoli beat Liverpool 3-0 at Murrayfield during pre-season and he gave Trent Alexander-Arnold a tough afternoon.
Football Italia are also reporting that Arkadiusz Milik is also set to miss the clash after suffering a setback.
The Polish international is only set to return to full training on Monday which is deemed too late to make the squad.
Milik was at the heart of the action when the two sides clashed at Anfield last December on match day six in Group C.
The forward was denied a stoppage time equaliser by Alisson Becker who blocked the shot with his outstretched right arm to send Liverpool through to the Round of 16 in second spot.
It proved to be a crucial moment on the road to the Wanda Metropolitano where the Reds lifted their sixth European Cup after beating Tottenham 2-0 on June 1.
Luckily for Ancelotti though, he still has plenty of attacking options at his disposal.
Mexican forward Hirving Lozano was snapped up for £34.2million from PSV and could prove to be one of the signings of the summer.
He could fill the void left in Insigne’s absence while Fernando Llorente could be handed a chance to shine.
The Spaniard move to Naples on a free transfer following his release from Tottenham at the end of last season.