Albion reached the semi-finals of last year's competition but suffered a painful penalty shootout loss to Manchester United at Wembley Stadium.
This Saturday's third round clash at Championship outfit Stoke is expected to be an opportunity for a number of fringe players and some exciting youngsters as De Zerbi continues to juggle his injury-hit squad.
The Seagulls are currently a very respectable seventh in the Premier League and have also qualified for the knockout stages of the Europa League, topping a tough group that featured Ajax, Marseille and AEK Athens.
The FA Cup offers another shot at sliverware for the Seagulls but a trip to Stoke in January is far from an easy assignment.
Here's the players who could be entrusted with the task as De Zerbi makes plenty of changes from the starting XI that drew 0-0 with West Ham in the Premier League on Tuesday night...
1. Bart Verbruggen - GK
The £16m summer arrival is expected to start ahead of Jason Steele for this one. Photo: Ryan Pierse
2. Jack Hinshelwood - RB
Slotted in very nicely at full back of late and his young legs should see him go again once more at Stoke. Photo: BEN STANSALL
3. Lewis Dunk - CB
The skipper should return for this FA Cup clash after serving a suspension at West Ham last Tuesday Photo: Julian Finney
4. Jan Paul van Hecke
One of Albion's best players of late and unlikely to be rested due to injury concerns to Igor and Webster Photo: Alex Pantling