Speaking to the Irish Independent, the singer claimed that the ITV talent show judge's behaviour is "excruciating" to witness.
She said of the Take That star: "That guy Gary Barlow, he has this horrible way of looking at people. If he was my son I'd be having a serious word with him about the way he's talking to people or treating people. I find it excruciating to look at.
"I don't think the people running the show are the kind of people who think about the effect of their behaviour upon people."
The 44-year-old admitted that she would worry if her teenage daughter auditioned for the show.
O'Connor added: "My daughter wants to be a singer. But I wouldn't want to put her into a situation like The X Factor where she would be vulnerable to being looked at by someone, which is a huge thing for a 15 or 16-year-old to deal with."
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Watch the video to Sinead O'Connor's defining 1990 hit 'Nothing Compares 2 U':