Both teams won their opening group games, with the Seasiders producing a 2-0 victory away to Barrow, while the Premier League youngsters overcame Morecambe.
Like the game at Holker Street last month, Neil Critchley is set to make a number of changes to his side.
Here’s our predicted XI for the game against Liverpool:
1. Who will start for Blackpool in the EFL Trophy tie against Liverpool U21s?
The Seasiders welcome the young Reds to Bloomfield Road on Tuesday night? Photo: CameraSport - Lee Parker
2. GK: Richard O'Donnell
Richard O'Donnell should be between the sticks on Tuesday night. The keeper has started in all of Blackpool's cup games this season. He helped himself to a clean sheet in the 2-0 victory over Barrow last month. Photo: CameraSport - Andrew Kearns
3. CB: Callum Connolly
Callum Connolly could return to the starting 11 for the game against Liverpool's youngsters. The defender featured from the bench in the draw against Charlton Athletic at the weekend. He can play a number of positions, and could be used as a wing-back as well as in the back three. Photo: CameraSport - Rob Newell
4. CB: Marvin Ekpiteta
Marvin Ekpiteta has lost his place in Blackpool's starting line-up in recent weeks. The EFL Trophy game with Liverpool will provide him an opportunity to rediscover his form. His last start was in the recent Central League game against Preston North End, but did come off the bench against Barnsley in League One. Photo: CameraSport - Andrew Kearns
5. CB: Doug Tharme
Doug Tharme could be handed another opportunity to impress in Tuesday's game. The defender's game time has been limited, but start the opening group game against Barrow. He will be hoping to make the most of the opportunity. Photo: CameraSport - Dave Howarth
6. RWB: Andy Lyons
Andy Lyons could make his return to competitive action on Tuesday night. The 23-year-old recently played in the Central League game against Preston North End, but was forced off with a head injury at half time. Photo: CameraSport - Andrew Kearns