The competition could be seen as a welcome distraction for the Terriers, following a run of bad performances which has seen the side go six league games without a win.
Boss David Wagner is all set to rest some of his key players as he did so in the previous round of the competition against Bolton Wanderers.
Birmingham beat fellow Championship side Burton Albion in the Third Round and currently sit 23rd in the table with Blues manager Steve Cotterill also likely to rest some of his key players with survival a more important objective.
Ahead of this weekend's clash, Daniel Rushworth analyses four of the most unforgettable clashes between the two teams…
Birmingham 2-0 Huddersfield Town, April 29th 2017
David Wagner's promotion chasing dreams led the German to playing a fully rotated team away to Birmingham in late April.
Jonathan Grounds scored just before half-time before a Craig Gardner penalty sealed the victory for the hosts.
Wagner's decision to rest key players with his sides play-off place secured would later be vindicated with the Terriers gaining promotion to the Premier League in May.
Birmingham City 0-1 Huddersfield Town, October 6th 2012
The forward's 25th minute strike enabled Town to leave the Midlands with all three points with the Terriers also helped by the dismissal of Birmingham striker Nikola Zigic.
Town eventually finished the campaign 19th in the Championship under the management of new boss Mark Robins, whilst Birmingham finished 12th.
Huddersfield Town 1-2 Birmingham City, May 6th 2001
On the final day of the 2000/01 season, defeat at home to promotion chasing Birmingham City saw Town relegated to Division Two.
A Curtis Woodhouse double either side of Andy Booth's 45th minute equaliser was enough to earn Birmingham three points and send Town down.
The defeat brought to an end a shocking season for the Terriers, having been so close to promotion to the Premier League the previous season under Steve Bruce.
Birmingham City 0-1 Huddersfield Town, October 21st 1989
Eoin Hand's Town travelled to St Andrews in October 1989 sitting sixth in Division Three.
Left winger Mark Smith earned Town a much deserved win, but Town would fail in their assault for promotion that season.
In the reverse fixture at Old Leeds Road ground, Town lost 2-1 and would finish eighth in the final standings one place and one point behind Birmingham.