The hosts reached the last eight of this competition last season before they were knocked out by runners-up Braga, while the visitors went a step further, reaching the semi-final, where they were beaten by the eventual cup winners Porto.
Match preview
After losing their first match of the season, Benfica have been formidable domestically and managed to regain top spot in the league standings just before the international break by beating Sporting Lisbon 2-1.
The Eagles found themselves a goal down in the first half of that match, but after Goncalo Inacio was shown red in the second period, they piled on the pressure and scored two goals in stoppage time to hand their arch-rivals their first league defeat of the season.
That result saw them extend their recent league record to 10 matches unbeaten, including nine wins, while the points they dropped in that time was at home in a 1-1 draw against Casa Pia last month.
Roger Schmidt's side beat Lusitania 4-1 in their only match in this competition to date, with Joao Mario, Rafa, Arthur Cabral and Tiago Gouveia all getting on the scoresheet as they cruised to an easy victory.
Unsurprisingly, Benfica have been the dominant side in this encounter over the years and come into this one unbeaten in their last 10 matches against this opponent, outscoring them 23-6 in that time.
Meanwhile, due to inclement weather that made it impossible to land in Madeira, Famalicao only played their third-round match against Camacha last week and eased past the lower league outfit 5-0.
With several changes made to the side, Francisco Moura, Gustavo Sa and Mihai-Alexandru Dobre all got on the scoresheet, while 19-year-old Pablo netted a brace to help book his side's progress to round four.
FCF are in seventh place in the Primeira Liga this season, with 16 points after 11 matches, and come into this one unbeaten in their last three in all competitions following a 3-1 win over Gil Vicente and a 0-0 draw to Vizela ahead of the international break.
Based on their record in this fixture, the visitors are likely to struggle to get past this round of the competition, though they cannot be written off entirely with their opponents likely to tinker with their team, with an important Champions League showdown against Inter Milan to come in midweek.
Benfica Taca de Portugal form:
W
Benfica form (all competitions):
L
D
W
W
L
W
Famalicao Taca de Portugal form:
W
Famalicao form (all competitions):
D
L
L
W
D
W
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Team News
Schmidt has been dealing with a few key absentees in defence, with Orkun Kokcu, Alexander Bah and Juan Bernat all missing through injury, though the latter is expected to return to action in the next week or two.
David Neres has missed the last four matches with a meniscus injury and is set to miss this one as well, which should see Fredrik Aursnes continue on the flank in a 3-4-3 formation.
In the opposing dugout, Joao Pedro Sousa has just one absentee in this match, with Theo Fonseca still recovering from a knee injury that has kept him on the sideline for the last five matches.
Chiquinho, Gustavo Sa and Jose Luis Rodriguez are expected to start in attacking midfield, while Mirko Topic and Zaydou Youssouf are likely to operate in the double pivot in front of the back four.
Benfica possible starting lineup:
Trubin; Silva, Otamendi, Morato; Luis, Neves, Aursnes, Neves; Di Maria, Silva, Cabral
Famalicao possible starting lineup:
Junior; Moura, Otavio, Riccieli, Nathan; Topic, Youssouf; Chiquinho, Sa, Rodriguez, Araujo
We say: Benfica 2-0 Famalicao
Benfica were in excellent rhythm ahead of the international break, and they will be looking for a solid result here to build up some momentum before their crucial Champions League clash against Serie A leaders Inter Milan next week. We are backing the hosts to secure the victory in this one.