The Ghanaian will not travel to Merseyside due to 'minor' knee injury, which similarly ruled him out of last weekend's 2-1 victory over Arsenal.
The setback is a blow to the 26-year-old, who is fighting to win back his place in the first eleven, having been displaced to the bench since the arrival of Kenedy in January.
"We have Atsu with a little problem, and we don’t want to take any risks at this stage," Benitez said.
“He has a knee problem. It’s just a little problem and he has had an injection, so we just have to be careful with him.
“It depends on his reaction as to whether he’ll play again this season.
"The plan is to keep him out of this game, see how he feels next week, and then see.
“If we have little problems, then we will try to protect the players if we can do it.
"We don’t want to take any risks with anyone when we don’t need to, so we’ll wait this week and see how he reacts.”
Atsu has made 28 league outings, involving 19 starts and two goals, for Newcastle so far this season.
He joined the outfit permanently in summer last year after helping the team secure topflight promotion during a loan stint from Chelsea.
He played for Everton in the 2014-15 campaign.