Group G: One point will see the defending champions Liverpool qualify for the last 16 for the third time in five seasons. But Real Betis will be no pushovers, even though their domestic form has seen them plunge to second from bottom in the Primera Liga.
Victory over Chelsea last month in Group G underlined their threat. And should Betis win at Anfield they have a great chance of getting to the last 16 themselves.
They have a final match at home to bottom club Anderlecht, while Liverpool would have to go to Chelsea and avoid defeat.
Liverpool manager Rafael Benitez, who still has injury doubts over Luis Garcia and Xabi Alonso, said: "We are not relaxed, we know our responsibility and that this will be a hard game. It is important we get through and then that will help us with our confidence in the Premier League.
"It is a dangerous situation for us, but more so for them because they need to win. A draw is no good for them."
Four successive victories with no goals conceded sees Liverpool high on confidence.
Betis lost a torrid local derby with Seville on Saturday which produced 14 yellow and two red cards. Their manager Llorenc Serra Ferrer is also in trouble for kicking a Seville official.
They have lost striker Ricardo Oliviera - whose goal beat Chelsea - for six months with a knee injury, and will also now be without another frontman, Dani Martin, who was injured against Seville.
Liverpool have conceded only six goals in their last 16 home European games and will have Harry Kewell, Mohamed Sissoko and John Arne Riise back in the squad.