The 21-year-old Belgian was forced off on a stretcher during Hoffenheim's 1-1 draw with Hertha Berlin on Sunday after colliding with opposition striker Adrian Ramos.
While Ramos was able to continue, Casteels was not and his chances of going to the World Cup - likely as a back-up for Thibaut Courtois and Simon Mignolet - look in the balance.
The club confirmed via their official Twitter account: "The suspected case of injury of @koencasteels...has unfortunately (been) confirmed: tibia fracture.
"He will be operated on (in) the evening in Berlin."
Former Genk player Casteels has been at Hoffenheim since 2011 and has represented Belgium at under-21 level.
While he is yet to make a senior appearance for Belgium, Casteels has been called up to previous international squads by coach Marc Wilmots.
‘The pure simplicity of the way Slot has managed the squad is probably the biggest thing I could say about him. It’s not broken, so let’s get on with it’: Liverpool legend full of admiration for Jurgen Klopp's successor at Anfield
‘I trained at Spurs and thought they’d give me a chance. But I received a letter thanking me but saying they didn’t think I was good enough – I was gutted’: How Tottenham missed out on signing Wales legend John Toshack
