Lampard was appointed as the Toffees boss on transfer deadline day and has had just a few days to work with his new team ahead of the visit of Brentford.
Everton needed extra-time to beat Hull in the last round while the Bees saw off Port Vale.
The Premier League rivals will be eager to go on a proper cup run but both may have an eye on the top-flight too as they battle the drop.
They have both been in poor form recently and a win the historic cup could kick-start their campaigns.
Everton v Brentford: talkSPORT coverage
This FA Cup tie will kick-off at 3pm on Saturday, February 5.
Commentary from Joe Shennan and former Arsenal and Everton striker Kevin Campbell.
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Everton v Brentford: Team news
Dominic Calvert-Lewin will miss Lampard's first match as Everton manager.
The England striker is out with a knock sustained in the loss to Aston Villa a fortnight ago while new signings Dele Alli and Donny Van de Beek are both cup-tied.
Abdoulaye Doucoure, Fabian Delph and Tom Davies are also out.
Centre-back Yerry Mina is in contention again after he returned from international duty with Colombia this week.
Brentford could welcome back first-choice goalkeeper David Raya for the trip to Merseyside.
The Spaniard has not played since he suffered a knee injury in October but featured in a friendly earlier in the week and will be assessed.
Deadline day signing Christian Eriksen is not in contention and will only train with his new team-mates for the first time on Monday.
Josh DaSilva has built up his fitness in recent friendly fixtures and may be part of the squad while Rico Henry and Mathias Jensen are available despite a nasty clash of heads during Brentford's loss to Wolves.
Julian Jeanvier, Mathias Jorgensen and Tariq Fosu are still absent.
Everton v Brentford: What has been said?
Frank Lampard acknowledges he has a tough job on his hands from the outset at Everton.
Speaking at his first press conference in the job, Lampard said: "In pure footballing terms we know we are in the position the club doesn't want to be in, but I have got a lot of belief in the squad.
"I have been watching the games closely from the outside, so I am under no illusions, but I believe we have a squad that can improve quickly.
"That starts with work on the training ground and the mindset of the group, but I understand in the short term the job is to improve our league position.
"In the long term, it is clear it is a club with big ambition, big history, a huge fanbase and a desire throughout to improve.
"There is a lot of work to be done but I am very proud to be given this opportunity to be at the front of it."