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Once the star recalled Prince Philip swearing at him for mistakenly taking his car.
The Queen rejected his interview requests three times, including once when she flatly stated she would never consider talking to him, according to Humphrys.
The journalist has also taken a few swipes at Prince Harry and Meghan over the years.
Humphrys, a self-professed “ardent republican”, has called for an end to the royals’ reign on a number of occasions.
John Humphrys took a swipe at Meghan Markle in an opinion piece questioning the Royal Family’s use
Meghan Markle and Prince Harry announced their departure from roles in the Royal Family last year
Humphrys highlighted the coronavirus pandemic meant the Firm was unable to travel to carry out as many royal duties.
He argued that COVID-19 had “deprived us of this service for a while”, which he downplayed as merely “hand-shaking”.
Humphrys continued: “As with everything else we’ve done without over the last few months, the question arises – do we actually need this service or can we do with less or even none at all?”
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Humphrys argued that the public could consider some royals “hangers on” and “leeches on the public purse”.
He continued: “Inheritors of ludicrous titles they do nothing to justify and expecting a deference they have done nothing to earn.
“‘Cull them!’ seems to be the cry of the knitters at the base of the guillotine.”
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He believed this could have “affected his attitude to the family profession”.
Humphrys then questioned why Meghan joined the Royal Family.
He said: “At least initially, it was supposed that in marrying him and joining the Royal Family, Meghan Markle fancied a bit of hand-shaking too.
John Humphrys clashed with Prince Philip when the royal was forced to sell his yacht
“Maybe she was misinformed.
“It would now appear that she thought she could become a duchess and an HRH without having to put on the white gloves.”
Humphrys countered his snipe at Meghan by questioning whether Harry wanted to marry outside of the Royal Family to allow him to leave the Firm.
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Humphrys added: “It wasn’t so much that Meghan married into the Royal Family as that Harry married into the family of Hollywood celebrity.”
He then mocked the lives of Meghan and Harry since their move to the US.
Humphrys said: “There’s not so much hand-shaking required over there.
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Humphrys’ remarks came as Harry and Meghan sought to establish financial self-sufficiency outside of the Royal Family.
The royal couple have negotiated deals with Netflix and Spotify, reportedly worth £81million ($ 112million) and £29million ($ 40million).
The Telegraph claimed they could earn up to £710,000 ($ 1million) for each public speaking event too.
John Humphrys presents Mastermind, which airs at 7.30pm tonight on BBC Two. His tenure as host will reportedly end after March.