2013 FA Cup winners Wigan Athletic are the last non-Premier League team remaining in this season's competition.
They've already taken out three Premier League sides this season, including a memorable victory over Manchester City in the last round. Southampton sacked Mauricio Pellegrino following defeat at Newcastle last weekend with Mark Hughes taking over until the end of the season.
Here is all you need to know as Wigan and Southampton aim to reach the semi finals at Wembley.
Wigan and Southampton have only met three times previously, with one win each and a draw. The last occasion came in February 2013, when both sides were struggled towards the bottom of the Premier League table.
Gary Caldwell put Wigan ahead but goals from Adam Lallana and Morgan Schneiderlin meant that Southampton took the lead. Shaun Maloney though would pop up with a crucial equaliser for Wigan.
The point wasn't enough for Wigan to come out of the drop zone and they would be relegated at the end of the season while Southampton finished 14th.
Wigan are top of League One having won their last match 1-0 away at Bradford on Wednesday night. They have only lost once at home this season, that being 2-0 to Blackpool last month.
Their FA Cup campaign began with victory over Crawley Town before they knocked out non-league side AFC Fylde. Since the third round, they've faced Premier League opposition beating Bournemouth in a replay, West Ham and then amazingly Manchester City.
Last weekend's 3-0 defeat to Newcastle saw the end for Southampton manager Mauricio Pellegrino, with Mark Hughes taking over. The Saints are one point clear of the relegation zone with the FA Cup providing some joy in a bitterly disappointing season.
Southampton have knocked out two Premier League sides, Watford and West Brom, to get this far as well as Championship outfit Fulham.
Chey Dunkley v Dusan Tadic
Wigan's famous win over Manchester City was built on a superb defensive display.
Chey Dunkley is having a brilliant first season at the club and he will hoping to stop Southampton's playmaker Dusan Tadic who Mark Hughes is hoping can pull the Saints out of trouble and to a date at Wembley.
Wigan will certainly be fancying their chances of a fourth Premier League scalp of the season especially given Southampton's poor recent run of form. However, the Saints will be eager to impress their new manager and this could prove to be one step too far for Wigan in their brilliant season
Prediction: Wigan 0-1 Southampton