Liverpool trail United, who have a game in hand, by seven points, but still cling to faint hopes of overturning the deficit and reclaiming a top spot they held for much of the first half of the season.
"It's a very important week," admitted Benitez. "If we can progress in the Champions League it's a boost for the next game.
"And if we can beat United we will still be in the title race. But if we don't it will be very, very difficult."
Liverpool will feel they have a great chance to progress in Europe after they scored a valuable away goal via Yossi Benayoun's header at the Bernabeu but Benitez has warned against complacency at Anfield.
"We must not think we are already there [the quarter-finals] or it will be easy," he added.
"But we have to approach the game with confidence. To win the tie is the most important thing. If we win the game it is done, but sometimes you don't need to win."
Benitez admitted it will be "difficult" for Benayoun, who has a hamstring problem, to play in the second leg, while defenders Daniel Agger and Philippe Degen are both unavailable and Albert Riera is suspended.
Doubts also remain over the fitness of striker Fernando Torres, who has not played since the first leg because of an ankle injury but took part in a light training session on Monday, and full-back Alvaro Arbeloa.
We have to have a lot of patience, make no mistakes at the back and the goal will surely come
Real defender Fabio Cannavaro
Nine-time champions Real Madrid - seeking a first quarter-final since 2004 - may take encouragement from the fact Liverpool have not won any of their last six home matches against Spanish clubs.
Real have improved significantly since the arrival of former Tottenham manager Juande Ramos in December and they come to Anfield full of confidence off the back of a recent 10-game La Liga winning streak, ended by a 1-1 draw with Atletico Madrid on Saturday.
However, Real defender Fabio Cannavaro has urged his side to be patient ahead of the game.
"We have to have a lot of patience, make no mistakes at the back and the goal will surely come," said the 35-year-old Italy international.
"If we score we would force Liverpool to come out and play. If they want to win the game they are going to have to play and this is the moment where we could take advantage."
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