Gloucester can consolidate their place at the top of Pool One with a back-to-back victory over English rivals London Irish.
The Cherry & Whites leapfrogged the Exiles with a thrilling 29-22 win at the Madejski Stadium in Round 3.
Freddie Burns contributed 24 points to the triumph and any hope of Irish claiming a victory at Kingsholm will hinge on stopping the England fly-half.
But the visitors have been dealt a blow with the loss of their Ireland scrum-half, a two-time Heineken Cup winner with Munster, to a back injury.
Irish can however call on Darren Allinson, who was a replacement in Cardiff Blues' Amlin Challenge Cup final triumph over Toulon in 2009.
Gloucester have been dealt a blow in the build up to the crucial clash with the news that their captain Jim Hamilton will quit the club for France in the summer.
But they have already bolstered their second-row options with the signing of Tongan giant Lua Lokotui.
Match Facts
• Gloucester have won five consecutive matches in the Amlin Challenge Cup and have lost just three of their last 19 in the competition.
• The Exiles have won eight of their last 10 Amlin Challenge Cup matches.
• The Cherry and Whites have triumphed in all three clashes between these teams in the history of the competition.
• Only Joe Carlisle (Worcester) has kicked more goals than Ian Humphreys (12) this season.