Littler came close to winning the sport’s biggest prize on his debut in the competition, and continued his remarkable rise by winning the Bahrain Masters last Friday.
He will now target success in the Premier League, but faces a tough opening against world number one and fellow Englishman Humphries.
They will meet in the last quarter-final in Cardiff, where home favourite Gerwyn Price will face Nathan Aspinall, Rob Cross takes on Peter Wright and seven-time winner Michael van Gerwen goes up against 2023 world champion Michael Smith.
All matches will be played over 11 legs, with Cardiff the first of 16 nights of Premier League action.
Ranking points are awarded on each night, with the top four players overall heading into the play-offs at London’s O2 on Thursday, 23 May.