His loved ones confirmed the news via his Instagram page.
"It is with a heavy heart that today we had to farewell our beloved Johnny. Surrounded by his partner Tahnee and family, Johnny went peacefully with the support of some incredible nurses and doctors," they said.
"He was a very talented, charming and sometimes cheeky boy. Johnny was very determined and had a strong will. He battled all the way to the end and fought as hard as he could. Such a beautiful soul with so much more to give.
"We all love you Johnny and will remember you for all the joy you brought to our lives. Rest easy."
Watch: Johnny Ruffo shares his story. Post continues below.
In 2011, a then 23-year-old Ruffo was a contestant on X Factor Australia where he won the hearts of the audience.
Soon afterwards he turned to acting, playing fan favourite Chris Harrington on Home and Away from 2013 to 2016.
Then in 2017, Ruffo shared that he had undergone surgery to remove a brain tumour. A week later, he announced he had been diagnosed with brain cancer and would be starting aggressive treatment. He was given the temporary all-clear from doctors, but in 2020, he was told the cancer had returned.