She gave $250,000 to Sydney couple Kristian and Rachel Anderson. Rachel is battling cancer and caught Oprah's attention when an emotional video Kristian made for his wife and featuring Hugh Jackman became a global internet sensation.
Oprah gave the couple a cheque so they and their two children could "take the year off and get well".
But the audience did not miss out either, with Oprah announcing that everyone would receive a silver necklace with an "O" pendant and a large South Sea pearl from north-western Australia in its centre.
Oprah also took time to speak directly to her fans after the show, telling them that "it means as much for me as it did to you for you to be here".
Oprah Winfrey Fever Hits Sydney
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