Edoardo Reja's men overcame their city neighbours 1-0 in last year's final at the Stadio Olimpico thanks to a goal from Bosnia-Herzegovina winger Senad Lulic.
And the capital club travel to the Stadio San Paolo knowing that victory in what is a matchup between the last two teams to win the tournament will force a repeat of the 2013 showpiece, but at the semi-final stage this time around.
However, the visitors face a Napoli side who have not suffered defeat in any competitions since a 3-1 UEFA Champions League loss to Borussia Dortmund in November.
That result sparked Napoli's current run of 10 games unbeaten, which began as Gonzalo Higuain's double inspired Rafael Benitez's side to a 4-2 win at Lazio.
And Napoli, who beat Atalanta 3-1 earlier this month to reach the quarter-finals, should be confident of replicating that display against a team who are without a win in their last four visits to Campania.
Defender Pablo Armero is a doubt for the hosts after missing the draw with Chievo due to illness, while Juan Zuniga is likely to miss out with a knee problem.
Long-term absentees Giandomenico Mesto (knee) and Valon Behrami (toe) remain on the sidelines.
Meanwhile, Lazio, 2-1 winners over Parma in the previous round, are without defender Stefan Radu due to hamstring injury.
Emiliano Alfaro (knee) and Ederson (hamstring) are unavailable, along with Stefano Mauri, whose match-fixing ban does not expire until next week.
A win would see Lazio take on bitter foes Roma three times in a week.
Reja's men face Rudi Garcia's side on February 9, a clash that would be sandwiched between a two-legged semi-final should the holders progress.
"We think game by game," Lazio's German striker Miroslav Klose said. "Now we think about Napoli, because we could play three derbies in a week."
