Saints, the holders, go to Featherstone; Bradford, the beaten finalists for the last two years, are at Rochdale; and Wigan, who won the Cup eight years running until 1995, are at Keighley.
The four amateur sides left in were all drawn at home. Ellenborough, who beat Bramley in the last round, await a visit from Hunslet, while Featherstone Lions, victorious at Doncaster, are at home to Hull KR. Egremont meet their professional Cumbrian neighbours, Workington Town, and the Halifax-based amateurs, Ovenden, host Salford from the Super League.
There are just two all-Super League Yorkshire derbies, with Leeds at home to Castleford and Halifax meeting Huddersfield.
"It could have been worse," said the new Leeds coach, Graham Murray. "Being at home is a slight advantage, but it is a major test for both clubs."
Anthony Sullivan, who played on the wing for St Helens in last year's Wembley triumph, described the tie at Featherstone as "a tricky one. The crowd there is right on top of you and they will make it very tough for us."
The Leeds-Castleford match will be the BBC's televised tie on Saturday with Featherstone likely to be the venue for the first ever live televised match on a Sunday.
SILK CUT CHALLENGE CUP Fourth round draw: Egremont v Workington; Barrow v Widnes; Lancashire Lynx v Dewsbury; Halifax v Huddersfield; Leeds v Castleford; Batley v London; Leigh v Sheffield; Wakefield v Warrington; Featherstone Lions v Hull K R; Ellenborough v Hunslet; Rochdale v Bradford; Swinton v York; Ovenden v Salford; Whitehaven v Hull; Keighley v Wigan; Featherstone v St Helens. (Ties to be played 14-15 February).Reuse content