Diagnosed with a brain tumour in November 2006, he refused to bow to his grim prognosis. He had five major operations before succumbing to the disease in Royal Prince Alfred Hospital.
In his final interview two days ago, Professor O'Brien said what mattered most to him was his standing in the eyes of his three adult children: "I just want my children to really know they knew their father well and they loved and admired him as a person. That's my only wish really."
He stated there were three things he wanted to get across: "The first is that I'm honoured to be recognised. Second is that, in my 30 years as a doctor and more than 20 years working as a specialist cancer surgeon, I really haven't achieved anything that was worthwhile by myself. I've been supported and assisted by many unselfish, dedicated people, the most important of whom has been my wife Gail.
"Thirdly, there are thousands of people in Australia who work quietly and humbly and who are very dedicated, who don't get recognised."
He said his work had prepared him for the disease and for death: "I think inevitably I'll die of this, and I'm not frightened of dying. I'm at peace with my situation, I'm not willing it to come quick but it will come soon enough."
Gail and his children were with him at the end.
Professor O'Brien, who was 57, led research into head and neck cancer in Australia and operated on hundreds of patients, including the Test cricketer Norman O'Neill and the Dragon lead singer Marc Hunter.
In that list I include my own dear mother who went to him in 1996 at the age of 87 with a tumour in her neck. Professor O'Brien operated twice on her aggressive cancer and then guided the radiotherapy, eventually telling her she was clear. He gave her another 10 years of life but most importantly he was a gentle, sensitive man in his caring for an elderly lady .
After the diagnosis he was unable to continue operating but instead worked for the establishment of Lifehouse, an integrated cancer centre, although he did not live to see construction begin.
Thank you Professor, you have left the world too early but you have left the world a much better place for your being here. I am sure you are admired, not just by your children, but by the Australian people and many others throughout the world. Enter gently into your rest.
Tributes are flowing in from colleagues, nurses with whom he worked, students he taught and, of course, patients as well as politicians.
This morning Prime Minister Mr Rudd, who became a close friend of Professor O'Brien during his work on Lifehouse, said he had made a "huge contribution to the Australian community" and would be "greatly missed".
"Chris transformed his personal adversity into a national opportunity, using his experience to fight so much harder for cancer patients and their families," he said.
"The Australian Government has offered the O'Brien family a state funeral in honour of Chris O'Brien's contribution to the nation. The O'Brien family advised me this morning that they would be pleased to accept this offer."
"It is only in exceptional circumstances that Governments offer state funerals; I believe Chris O'Brien has been a truly exceptional Australian."