The former Free State Cheetahs and Blue Bulls forward was first diagnosed with the illness during the early 2000s at the end of a successful career that saw him earn 36 Springbok caps, while he was also one of the stars of the team that lifted the William Webb Ellis Trophy on home turf 15 years ago.
Kruger, who was just two months short of his 40th birthday, made his debut against Argentina in Buenos Aires during 1993 and was named South African Rugby Player of the Year in the same year that the country won the World Cup.
"Ruben Kruger was the epitome of the Springbok flanker, tough, indomitable and with an outstanding work ethic," said Oregan Hoskins, president of the South African Rugby Union (SARU). "When Ruben was on the field you always knew that the Springboks would not be beaten without a tremendous battle.
"Our prayers have been with him through his battles against illness and it is very sad to hear of his early passing. Our thoughts are with his young family and we extend to them our sincerest condolences."
The Blue Bulls regarded Kruger, a tough, ball-winning loose forward, as one of the best flankers ever to play for the club. "Apart from his rugby playing abilities, he has been a superb human being and everyone that knew him will surely miss him in the months and years to come," said the Bulls in a statement.
Nicknamed the "Silent Assassin" by Springboks coach Kitch Christie during the 1995 Rugby World Cup, he scored a controversial try in the semi-final played in a deluge against France in Durban but was denied what appeared to be a certain try by referee Ed Morrison in the Ellis Park final in Johannesburg. It didn't stop South Africa recording a dramatic 15-12 extra-time win over the All Blacks. Kruger battled back from a broken leg he suffered in a Tri-Nations match in 1996 to earn a call-up to the 1999 World Cup squad, and fought his recurring illness with typical bravery.
Kruger made his final appearance for the Boks against New Zealand in 1999 and after rugby became a camera salesman.
Kruger battled the brain tumour since 2000, which was diagnosed after he blacked out during a match.
An initial operation to remove the tumour appeared to have been successful, but the tumour resurfaced. Throughout his illness, Kruger battled against it with a strength that was a hallmark of his playing days.
Sadly, the tumour was too sensitively placed to completely remove, and it resurfaced in June last year when he blacked out while driving and was involved in a car accident.
This past week Kruger, started to feel unwell again and was admitted to hospital in Pretoria before his death on Wednesday. Kruger, originally from Vrede in the Free State, is survived by his wife Lize and daughters, Zoe and Isabella.