The eye-catching clash of the round, where all fixtures start a minute late to highlight a mental health campaign, is tomorrow’s Merseyside derby as runaway Premier League leaders Liverpool host Everton, who have shown a noticeable improvement since Carlo Ancelotti took over.
However, the dreamers who hold onto the idea of the 'romance of the cup' will be hopeful of giant killing exploits by the underdogs and here AFP Sport picks out three matches to justify the tag.
Rochdale (League One) v Newcastle United (Premier League). Saturday (Kick-off: 12:31pm GMT)
Rochdale may be a lowly 18th in the third tier but based on their recent FA Cup record compared to Newcastle's they can entertain genuine hopes of claiming a major scalp.
Rochdale have reached the fourth round of the competition in four of the last six seasons which is one more than Newcastle have.
The Magpies travel to Rochdale with their morale at a low ebb following a 3-0 home hammering by Leicester which was their fourth defeat in five matches.
Adding to manager Steve Bruce's problems is an injury crisis. Four players including captain and most impressive performer this term Jonjo Shelvey went off during the Leicester defeat taking their total of injured personnel to 11.
Rochdale's young Irish manager Brian Barry-Murphy has been praised for his side's style of play and victory over the old campaigner Bruce could attract more high profile clubs to the 41-year-old's qualities.
The pressure is on Bruce to secure a morale boosting and much-needed win.
“We have had a bad week. We have to put it right and get ready for the FA Cup at the weekend,” he said.
Sheffield United (Premier League) v Fylde (National League). Sunday (Kick-off: 2:01pm GMT)
The non-league team have quite a task travelling to take on the Blades who are acquitting themselves well back in the top tier.
The 'Coasters' have beaten fellow non-league outfits Nantwich and Kingstonian in the previous rounds to reach this stage of the competition for the first time but this is a huge step up for the side in the relegation zone of the fifth tier of English football.
However, United lost to another National League side Barnet last season at the same stage.
Several of the squad including defender Andy Taylor will be familiar with the hosts having played for them.
Taylor, who was a United regular in the Championship in 2009 but failed to win back his place after 14 months out with a serious injury, says they travel with belief they can pull off a major shock.
“It's one I look back on with great fondness, playing at that level in a great stadium. There's always an upset, so you never know, we'll be confident, positive and will give a good account of ourselves,” said the 33-year-old.
Gillingham (League One) v West Ham United (Premier League). Sunday (Kick-off: 6:16pm GMT)
The Gills are just three points off the play-off places in League One and have an imposing recent home run under the experienced Steve Evans - seven wins and a draw in their last eight matches at Priestfield Stadium.
Giving the hosts extra hope of an upset is that the Hammers have been beaten by lower league opposition in cup competitions both last season, AFC Wimbledon humbling them 4-2 in the FA Cup, and this term when Oxford United embarrassed them 4-0 in the League Cup.
However, the London side go into the tricky tie on the back of a 4-0 thrashing of fellow Premier League strugglers Bournemouth in David Moyes' first match of his second spell in charge.
Who comes out on top may depend on whether Moyes picks a first choice team or keeps them fresh for their next league game on Friday week (Jan 10) away at Sheffield United.