Hughes has received a positive test result for Covid-19, and is subsequently self-isolating at home.
As a result, he will not be able to compete in the Players Championship Finals, which will take place from November 26-28 at Butlin's Minehead Resort.
Hughes will be replaced directly in the draw bracket by Klaasen, who is the next highest-ranked player from the 2021 Players Championship Order of Merit who was not already in the event.
Klaasen will make his tenth Players Championship Finals appearance against fellow Dutchman Vincent van der Voort as their first round meeting takes place on Stage Two on Friday evening.
The Ladbrokes Players Championship Finals will be broadcast on ITV4 in the UK, through DAZN in various worldwide territories, via RTL7 in the Netherlands and the PDC's global broadcast partners.
PDCTV coverage on Friday and Saturday from Stage Two will be available worldwide.
2021 Ladbrokes Players Championship Finals
Friday November 26
First Round
Afternoon Session (1245 GMT)
Main Stage
Ryan Searle v Simon Whitlock
Krzysztof Ratajski v Ron Meulenkamp
Michael Smith v William Borland
Joe Cullen v Andy Boulton
Dimitri Van den Bergh v Madars Razma
James Wade v Ricky Evans
Nathan Aspinall v Jeff Smith
Adrian Lewis v Kim Huybrechts
Stage Two
Scott Mitchell v Martijn Kleermaker
Ryan Joyce v Luke Woodhouse
Martin Schindler v Ian White
Mervyn King v Darius Labanauskas
Brendan Dolan v Chas Barstow
Ross Smith v Rusty-Jake Rodriguez
Danny Noppert v Rowby-John Rodriguez
Gabriel Clemens v Steve Beaton
Evening Session (1900 GMT)
Main Stage
Stephen Bunting v Gary Anderson
Raymond van Barneveld v Maik Kuivenhoven
Rob Cross v Jermaine Wattimena
Jose de Sousa v Devon Petersen
Gerwyn Price v Jason Lowe
Michael van Gerwen v Kevin Doets
Peter Wright v Keane Barry
Jonny Clayton v Alan Tabern
Stage Two
Vincent van der Voort v Jelle Klaasen
Daryl Gurney v Alan Soutar
Damon Heta v Steve Lennon
Callan Rydz v Mensur Suljovic
Dirk van Duijvenbode v Ryan Meikle
Luke Humphries v Jason Heaver
Chris Dobey v William O'Connor
Dave Chisnall v Ritchie Edhouse
Saturday November 27
Afternoon Session (1245 GMT)
Main Stage
8x Matches TBC
Stage Two
8x Matches TBC
Evening Session (1900 GMT)
Third Round
Main Stage
4x Matches TBC
Stage Two
4x Matches TBC
Sunday November 28
Afternoon Session (1245 GMT)
Main Stage
Quarter-Finals
Evening Session (1900 GMT)
Main Stage
Semi-Finals
Final
Plus PDC Unicorn World Youth Championship final