Hull beat Middlesbrough 2-0 in the third round to reach this stage, but that is their only victory in their four matches in 2014 so far having lost to Liverpool, Chelsea and Norwich City.
That has left the Tigers 11th in the Premier League table, just five points clear of the relegation zone in a tight bottom half.
The victory over Middlesbrough was their only win in their last 10 games on their travels, a run that has seen them score just eight goals and concede 16.
In the opposite dugout from Bruce will be Phil Brown, who spent four years as manager of Hull, guiding them into the top flight in 2008.
He is attempting to gain promotion again this season and his side are well placed to do so, sitting fifth in League Two and just one point off the automatic promotion spots.
The Shrimpers have not made the fifth round of the FA Cup for more than 20 years, but a resounding 4-1 victory over Championship side Millwall in the last round will give them plenty of confidence ahead of Saturday's match.
They will also be flying high due to their recent form, which has seen them go seven games without defeat and lose just one of their last 15 matches in all competitions.
However, they have never beaten Hull before, losing four and drawing one of their five meetings in the past.
Possible starting lineups
Southend: Bentley; Timlin, Prosser, Phillips, O'Neill; Leonard, Hurst, Atkinson; Straker, Coker, Corr
Hull: Harper; Figueroa, Bruce, Davies, El Mohamady, Rosenior; Livermore, Koren, Meyler; Jelavic, Long
Sports Mole says: 1-2