Megan Malone (5) died from a rare and aggressive form of brain cancer.
Megan's plight touched hearts across Ireland and the US -- and her death came despite indications last Christmas that she had beaten her condition thanks to pioneering treatment in New York and Boston.
Her death came after her condition suddenly got worse and she had to return from her Kilnamartyra home in Cork to the US for emergency treatment.
Megan's father, John, said words could not describe their devastation.
"Our beautiful little princess Megan lost her brave fight for life last night. She battled her terrible disease for over 26 months and it finally got the better of her little body and soul.
"We are so, so devastated I cannot detail her passing right now. Words for once will not come out. Our hearts are truly broken. No more suffering, No more pain. Poor, poor little darling Megan, may you rest in peace," he sobbed.
Megan's mother, Sheila, was too upset to comment.
The little girl's aunt, Aine Watts, said the timing of Megan's death was particularly cruel.
"We are all devastated by the news. The entire family and extended family are devastated by losing Megan who was so, so brave."
In October 2010, Megan was diagnosed with a rare brain cancer called a SPNET-Medullablastoma.
The cancer had spread to Megan's spine and surgeons told her family that the condition had just a 20pc survival rate.
The Malones decided to bring Megan to the US for pioneering treatment, including blasting her tumours with proton beams.
She went to New York's Presbyterian Hospital in January 2011 and, together with a facility in Boston, received nine months of intensive treatment.
Megan was allowed back to Ireland in September 2011 amid indications that her cancer was in full remission.
The family were rocked last January when doctors confirmed that the cancer had returned.
Despite treatment, Megan's condition began to weaken in October.