Mining magnate Andrew "Twiggy" Forrest and his wife Nicola are donating $400 million to be used for a number of causes, including cancer research and the eradication of slavery.

The donation was described by Prime Minister Malcolm Turnbull as the "the biggest single philanthropic gift" in Australian history, and the largest donation by a living Australian.

How will the money be spent? $75 million coordinating world cancer institutes to eliminate deadly cancers

$75 million coordinating world cancer institutes to eliminate deadly cancers $50 million to "build stronger communities"

$50 million to "build stronger communities" $75 million for higher education and breakthrough research

$75 million for higher education and breakthrough research $75 million to "give every child their best chance"

$75 million to "give every child their best chance" $50 million to "create equal opportunities for all Australians"

$50 million to "create equal opportunities for all Australians" $75 million to end modern slavery

Mr Forrest, the founder of mining company Fortescue Metals, is estimated by Forbes to have a net worth of more than $5.5 billion.

Mr and Ms Forrest have a long history of donating to philanthropic causes.

"I have been very fortunate, with my wife, Nicola, to be able to accumulate capital, and then as soon as we can to commence giving it away," Mr Forrest said.

"We had a slightly unsustainable business model previously, where we would actually borrow money to give it away.

"Fortunately, we don't have to do that now, thanks to the strength of the iron ore sector."

Mr Turnbull said the money would be put to a range of initiatives, including fighting cancer, investing in higher education, and ending slavery.

Malcolm Turnbull and Russell Crowe attended the announcement in Canberra. ( ABC News: Marco Catalano )

"It is a game-changer in the Australian philanthropic community. And it will change the lives of thousands of people here in and around the world," Mr Turnbull said.

"But all of us should seek to do as much as we can with what we have. So, this is real leadership and leading by example."

The University of Western Australia, which has benefited from Mr Forrest's philanthropy in the past, will receive $75 million of the donation.

Vice-chancellor Dawn Freshwater said the money would be used to attract the best talent to the university.

"We see this as an opportunity to build a powerhouse of activity in areas that are really going to be life-changing and making a real difference to the communities both locally, regionally, nationally and internationally," she said.

Mr Forrest was the Western Australian nominee for the 2017 Australian of the Year for his work in highlighting Indigenous disparity and advocating for the end of modern day slavery.

While today's donation is the largest made by living people, in 2014 healthcare and media entrepreneur Paul Ramsay left about $3 billion to his personal foundation when he died.