Goals from Sonny Carey and Kylian Kouassi helped the Seasiders to a 2-0 victory over Barrow in their opening group game.
Like the fixture at Holker Street, Neil Critchley is set to make changes to his side for the visit of the Premier League youngsters.
Here are some of the players who could be handed an opportunity:
1. Who should be handed an opportunity in tonight's EFL Trophy tie?
Blackpool welcome Liverpool U21s to Bloomfield Road. Photo: CameraSport - Lee Parker
2. Jake Beesley
It's been a hit and miss start to the season for Jake Beesley. He started the first number of games for the Seasiders, and even scored a brace in the EFL Cup tie against Derby County, but has missed out in the last few weeks. There have been some positives to take from his performances, and the Liverpool U21s game could be a great opportunity for him. Photo: CameraSport - Andrew Kearns
3. Marvin Ekpiteta
Marvin Ekpiteta regularly featured in Blackpool's starting line-up at the beginning of the season. A drop off in form and a couple of errors has seen him fall behind some of his teammates. He's proven his quality in defence, and the Liverpool U21s fixture could be a chance for him to find his feet again. Photo: CameraSport - Andrew Kearns
4. Andy Lyons
Andy Lyons will be looking to forge a way back into the Seasiders starting 11. The 23-year-old missed a couple of games due to personal reasons last month. He featured in the Central League fixture against Preston North End, but was forced off after being involved in a clash of heads. Photo: CameraSport - Andrew Kearns
5. Tashan Oakley-Boothe
Tashan Oakley-Boothe joined the Seasiders on a free during the summer following his departure from Stoke City. It's been a slow start for the midfielder so far, who has been building up his fitness after missing pre-season. He has appeared in a few of the cup games as well as the Central League clash against Preston North End. Photo: CameraSport - Andrew Kearns
6. Doug Tharme
Doug Tharme started the EFL Trophy opener against Barrow and put in a solid performance. He was subbed off in the second half after picking up a yellow card. Photo: CameraSport - Dave Howarth