Top seed and defending champion suffered his sixth match loss of a season on Tuesday in his second RR match at the Barclays ATP World Tour Finals.
Nole came up against his toughest test this week, but prevailed to clinch a 7-6 (3), 7-6 (8) victory in two hours and seven minutes.
The top seed from Serbia enjoyed a crushing 6-2, 6-2 victory over John Isner (USA, 6) to book his place in the China Open last on Friday.
Novak's straight sets win over ninth seed Marin Cilic earned him his 50th career victory at the All England Club. He will face Richard Gasquet on Friday.
Top seed lost first two sets but fought back to beat Kevin Anderson 6-7 (8), 6-7 (8), 6-1, 6-4, 7-5 and reach the last 8.
Defending champion beat German Philipp Kohlschreiber in two hours and two minutes on Monday to reach the second round.