The popular broadcaster spent the last few years finding out as much as he could about the fate of some 40 children to, as he put it, “free them of the anonymity”.
The children, aged 16 and under, were among 374 civilians killed during the six days of the insurrection.
Hachette Books Ireland commissioning editor, Ciara Considine, said they were delighted to be publishing a “fascinating” work.
“Joe Duffy has undertaken extensive research, uncovering much new material and the book promises to offer the most comprehensive narrative to date on the subject of children and the 1916 Rising.”
Mr Duffy said the stories of the children who died during the six days of fighting remained untold to this day.
“I am very pleased to shine some light on their short lives, in the context of an intense period in Irish history when Dublin was the single most dangerous place in the world for young people,” he said.
The book, to be published in October, will also describe city life 100 years ago when families lived in tenements, poverty was rife and children spent much of their time on the city streets.
Last April a memorial service was held for the children in Dublin during which local children held up cardboard signs with the names of the children killed during Easter 1916.
The service in the Church of the Immaculate heart of Mary in City Quay was attended by families of 15 of the dead children.
Mr Duffy, who played a leading role in organising the service, said at the time that its purpose was “just to remember and reclaim”.
He made a public appeal when he started finding out about the children who died — two were aged 2.
His painting of children scavenging in the ruins off Sackville Street was on display the GPO in Dublin until the middle of January last year, together with a special free postcard listing the names and known addresses of the children.