In the course of a public appearance to a cathedral in Staffordshire on the start of the week, King Charles was confronted by a man who questioned him about his brother's relationship with disgraced financier Epstein.
The protester inquired how long the monarch had been known about his brother's association with Epstein, and also questioned whether he had asked the police to "hide" for Andrew.
Despite the protest, there were large groups of fans and cheers for the King, who was in Staffordshire for an ceremony.
The Duke of York's links with Epstein have been under intense scrutiny in the past few weeks. The royal, who relinquished his titles earlier this month, has categorically denied any misconduct.
"For how long have you known about Andrew and Jeffrey Epstein? Did you request the authorities to cover up for Andrew?"
The monarch ignored the questions but carried on meeting supporters, some of whom chanted "Long live the King". One fan can be heard requesting him for a hug.
A female bystander outside the cathedral was also observed telling the protester to "go away" and to "be quiet".
The controversy over the Duke of York's connections to Epstein has been reignited by sexual abuse allegations repeated in Ms. Giuffre's posthumously-published memoir.
In the memoir, Ms Giuffre alleges she had sex with the royal on three separate occasions, including once with Epstein and "eight other young girls"
Andrew, who agreed to a financial settlement with Ms Giuffre in recent years, has repeatedly denied any wrongdoing. In a previous interview, he told BBC Newsnight he did not recall meeting Ms Giuffre "ever", and that they "did not have any sort of intimate relations."
But recently, new inquiries have been raised about how he is able to fund his lifestyle despite not being a active member of the royal family.
The revelation that he has only ever paid a token annual rent on his Royal Lodge has intensified the scrutiny over his living arrangements - even though he made large payments up front, including for improvements.
The Liberal Democrats said he should be summoned before members of parliament to give testimony about his rental agreement of his lodge.
But last week, the government refused to give MPs time to discuss the royal's status or his residence, despite growing pressure for scrutiny.
The royal household has not commented on whether the Duke of York might relocate of his current residence - or where he might reside.
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