In the season 2004-2005, Paul Hunter reached the semi-finals of the Grand Prix, where he lost to Ronnie O’Sullivan (3-6). Just before competing in the China Open, where he got through to the quarter-finals, Hunter received the devastating news that he was suffering from malignant neuroendocrine tumours (unknown causes). A spokesman for the World Professional Billiards and Snooker Association said at the time: "Paul will undergo treatment (chemotherapy) to cure himself of this illness. He would like to reassure his fans and supporters that, as with his snooker career, he is tenacious and positive in his fight against the disease."
In 2005, Hunter returned to play in the Grand Prix, but lost to Rory McLeod in the first round. At the UK Championship, Hunter won the match against Jamie Burnett (9-8), but lost the one against the eventual champion Ding Junhui.
On 26 December 2005, Paul Hunter and his wife, Lindsey, became parents to their first and only child, daughter Evie Rose.
Hunter’s last ever match was against Neil Robertson, in the first round of the 2006 World Championship, where he lost 5-10. Hunter admitted that he was worse than the previous year (when his world ranking was of 5) and that he had been in continuous pain. On 27 July 2006, the WPBSA confirmed that, following a members' vote, the organisation's rules would be changed to allow Hunter to sit out the entire 2006/2007 season with his world ranking frozen at 34. He intended to devote the year to treatment for his cancer.
On the 9th of October 2006, Hunter died at 8:20 pm– just five days short of his 28th birthday – at the Kirkwood Hospice in Huddersfield. His funeral took place on 19 October 2006 at Leeds Parish Church. Many players attended the ceremony, and his best friend, Matthew Stevens, was a pallbearer at the service. At the Premier League Snooker matches on the 12th of October 2006, a moment of silence was kept in his honour.
Stephen Hendry, Mark Williams, Jimmy White, Matthew Stevens and Ken Doherty put forward the request that the Masters trophy to be named after Hunter in his memory. Instead, the Fürth German Open, a tournament first won by Hunter, was renamed the Paul Hunter Classic.
The Paul Hunter Foundation was set up after his death to give disadvantaged children places to play sport and socialise.
In 2006, Paul Hunter was awarded posthumously the BBC Sports Personality of the Year Helen Rollason Award.

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