James damaged a thigh muscle on duty with Colombia last week and will probably be sidelined for around a month and Isco played in his place in Saturday's 6-0 La Liga success at Espanyol and is likely to do the same in Tuesday's Champions League Group A opener at home to Shakhtar Donetsk.
While James has two goals in two appearances this term, to add to the 17 he netted last season, Isco has yet to score in his three games and only managed six in 2014-15.
"Isco is a great footballer and what he needs to do is to carry on doing what he has been this whole time," Benitez told a news conference previewing the clash at the Bernabeu.
"Work, work with intensity and dedication and beyond that make the most of the quality he has to score the odd goal more," added the 55-year-old, who took over from the sacked Carlo Ancelotti at the end of last season.
"I am very interested in the contribution he makes in terms of effort and balance and if he is more effective in front of goal that is better for everyone."
Real, the record 10-times European champions who last won the continent's elite club competition in 2014, were in electric form in their two most recent La Liga outings. They hit five without reply past Real Betis and followed up by hammering Espanyol when Portugal forward Cristiano Ronaldo netted five goals to become Real's record scorer in La Liga.
Ronaldo is also the joint leading marksman in the Champions League with 77 goals alongside Barcelona forward Lionel Messi and Shakhtar and their Romanian coach Mircea Lucescu could be in for a rough ride on Tuesday.
Real have only failed to win their opening home match twice in 45 European Cup campaigns and not since 1962 when they drew 3-3 against Anderlecht.
"They are a great team with a very experienced coach who always gets the best out of his new players," Benitez said.
"They have players with ability, quality and speed and if we are not very focused and do not take the game as seriously as we should we could find it difficult."
COMMENTS
Comments are moderated and generally will be posted if they are on-topic and not abusive.
For more information, please see our Comments FAQ