Red Devils 20:00 Saints
Two former winners of the Challenge Cup go head-to-head on Sunday, as 1998 winners Sheffield travel to Rovers, who won the Cup in 1980.
1998 Lance Todd Trophy winner Mark Aston has been in charge of the Eagles since their re-formation in 1999, and has led them to two Championship titles as well as a top four finish in 2015.
Despite a difficult start to the season which has seen them slip to tenth in the Championship table, their 32-14 win over Toulouse last month will give them hope of knocking off their full time opponents.
But Hull KR, 2015 Challenge Cup finalists, will be wary of suffering another shock reverse after their loss at home to Oldham at the same stage of the competition last year.
Dewsbury Rams welcome Newcastle Thunder to the Tetley's Stadium on Friday night and the visitors will be hopeful of shaking up their hosts.
The 2016 League 1 Shield winners have won their last 14 games, while Dewsbury have endured a torrid time of late, losing all of their matches in 2016.
Mick Mantelli's side will travel to West Yorkshire with confidence and a point to prove after slipping to a 28-18 defeat at the Rams in the fourth round of the Challenge Cup two years ago.
Haydock, the only community club left in the Challenge Cup, are aiming to pull off arguably the biggest upset in the Cup's history on Saturday.
The Yickers are the lowest-ranked team ever to make it to the fourth round and they sit 71 places behind Oldham, their hosts at the weekend.
They sealed their place in the Challenge Cup after beating Thatto Heath Crusaders' A team 23-14 in the North West Men's League Premier Division Grand Final.
They stunned Wath Brow Hornets with a 17-4 away win in round one, before a 30-20 win over Thornhill Trojans set up a trip to London's Wests Warriors.
Though Wests had claimed their own scalp in round two, knocking off Featherstone Lions 26-0 away from home, Haydock strode into round four, and a place in history, thanks to a 26-12 win.
@HaydockOA What an achievement to make it this far in the challenge cup. Wishing you guys all the very best this weekend ✊🏽— Mose Masoe (@MoseMasoe) March 14, 2017
Friday, March 17
London Broncos v Toronto Wolfpack (8.00pm)
Dewsbury Rams v Newcastle Thunder (8.00pm)
Saturday, March 18
Oldham v Haydock (1.00pm, BBC Sport)
Toulouse Olympique XIII v Batley Bulldogs (2.30pm)
Swinton Lions v London Skolars (3.00pm)
Barrow Raiders v Keighley Cougars (6.30pm)
Sunday, March 19
Whitehaven v Oxford (2.00pm)
Hull Kingston Rovers v Sheffield Eagles (3.00pm)
Bradford Bulls v Featherstone Rovers (3.00pm)
University of Gloucestershire All Golds v Doncaster (3.00pm)
York City Knights v Rochdale Hornets (3.00pm)
Halifax v Hunslet (3.00pm)
Tickets for the 2017 Ladbrokes Challenge Cup final at Wembley Stadium on Saturday, August 26 can be purchased by calling the Rugby League Ticket Office on 0844 856 1113 or by visiting rugby-league.com/tickets.