Federer, the 17-time major champion who is chasing a record sixth US Open title, has a 5-0 career edge over Cilic including a four-set win in New York in 2011 and at Toronto in three tough sets last month.
Cilic, the 25-year-old 14th seed, missed last year's US Open sitting out a controversial doping ban handed out after he tested positive for a banned stimulant contained in a supplement bought over-the-counter by one of his staff.
"It angered me how all the process went because it was not fair to me. It wouldn't be fair to any tennis player," Cilic said.
Cilic was a semi-finalist at Australia in 2010 and a two-time quarter-finalist in New York in 2009 and 2012.
But that final step has always proved impossible for Cilic, who now has 2001 Wimbledon champion and compatriot Goran Ivanisevic in his corner as coach.
Federer, the champion from 2004-2008, reached his ninth US Open semi-final but first since 2011 with a dramatic 4-6, 3-6, 6-4, 7-5, 6-2 win over France's Gael Monfils, saving two match points in the process.
"I'm looking forward to playing Marin," said Federer. "He's a great guy. We had a tough, tough match in Toronto. I think I needed nine match points to close him out and beat him at midnight, 6-4 in the third, so we know what to expect."
Federer has already improved on his last two visits to New York -- a quarter-final exit to Tomas Berdych in 2012 and a dispiriting fourth-round loss to Tommy Robredo 12 months ago.
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