The Wolves have won the trophy three times in the last four years and will be starting out against the part-time Cougars for the third year in a row. Twelve months ago Tony Smith's men won 44-18 at Cougar Park and they triumphed 80-0 at the Halliwell Jones Stadium in 2011.
"The challenges of going to Keighley are different and we look forward to it, having experienced it before and knowing a little bit more than we did last time," Smith said. "They are dangerous games. Teams from the lower division grow a leg or two with nothing to lose and a whole lot to gain."
Smith is considering giving first appearances to Glenn Riley and Danny Bridge while Warrington's young prop Ben Evans will make his debut for Bradford in their fourth-round tie at Rochdale.
The Welsh forward joined the Bulls in December on a season-long loan and is now fit to resume his career after being frustrated by a hip problem which required surgery.
"Ben needs to play and this weekend will be a good one for him," Bradford coach Francis Cummins said. "He's been through the toughest part of his career. There's nothing worse than being injured and being out for a long time. It's worse when you only just start to feel part of a group but you can't chip in and help out your mates because you're injured."
Huddersfield may also take the opportunity to blood a youngster against Kingstone Press Championship opposition. Prop Nathan Mason has been called up for the short trip to Batley, along with Tongan forward Ukuma Ta'ai, who will make a first appearance for five weeks.
North Wales Crusaders coach Clive Griffiths has set his side the target of improving on last year's 98-4 hammering by Wigan when they take on Hull at the KC Stadium. The match will see Hull prop Paul Johnson going up against his brother Tommy, the Crusaders full-back.
Hunslet will be without their Leeds' dual-registered players Jimmy Keinhorst and Richard Moore for the visit of Catalan Dragons, who are set to field almost a complete team of Frenchmen. Toulouse will hope to make it a French double in Monday's fifth-round draw when they take on York, who only just edged out amateur side Blackbrook in the last round.
Alan Hunte will take charge of Salford for the last time before Brian Noble moves in against the University of Gloucestershire in Cheltenham. The Championship is guaranteed representation in the last 16 with Barrow going to Halifax and Whitehaven hosting Workington in an eagerly-anticipated Cumbrian derby.