While the Croatian's ambitions hang in the balance, his victory over Isner at the 02 Arena in south-east London propelled the top seed Novak Djokovic into the last four.
He saw off the third seed Alex Zverev 6-4, 6-1 to register his second win in the Guga Kuerten pool.
Djokovic, who is seeking a record equalling sixth crown at the eight man end of season championships, will play Cilic who is appearing for the fourth time at the championships.
After only his second success in 11 matches at the event, Cilic said: "I started to feel the ball really well in the second set. I was playing great tennis towards the end."
On Thursday, in the final round of games in the Lleyton Hewitt group, second seed Roger Federer will take on the fourth seed Kevin Anderson while seventh seed Kei Nishikori will face the sixth seed Dominic Thiem.