A Buckingham Palace statement said late Sunday: "The Duke of York has been appalled by the recent reports of Jeffrey Epstein's alleged crimes.
"His Royal Highness deplores the exploitation of any human being and the suggestion he would condone, participate in or encourage any such behaviour is abhorrent," the BBC reported.
The statement comes after the Mail newspaper on Sunday published footage which claimed to show the Duke of York inside the late financier's Manhattan mansion in 2010.
Epstein, 66, committed suicide on August 9 while awaiting federal trial for sexually exploiting girls as young as 14.
He was accused of paying girls under the age of 18 to perform sex acts at his Manhattan and Florida mansions between 2002 and 2005. Epstein however, pleaded not guilty to all the accusations levelled against him.
The Duke was photographed with Epstein in New York's Central Park in 2010 and his former friendship with Epstein, who was sentenced to 18 months in prison in 2008 for soliciting a minor for prostitution, attracted criticism at the time.
Buckingham Palace had previously denied claims that Prince Andrew groped a woman in Epstein's US home, the BBC reported.
The accusation was made in documents from a 2015 defamation case.
Meanwhile, another of Epstein's accusers has claimed that she was forced to have sex with the Prince on three occasions between 1999 and 2002, when she was under-age according to US law.
Buckingham Palace has branded the allegations "false and without any foundation", stating: "Any suggestion of impropriety with under-age minors" by the Duke was "categorically untrue".
( With inputs from IANS )