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Heughan, who plays Highlander Jamie Fraser in the show based on the Jacobite rising, voiced fears over its impact on locations such as Culloden near Inverness and Doune Castle in Perthshire.
The ‘Outlander effect’ has been credited with boosting Scotland's economy with fans flocking to see sites used as filming locations for the show.
The 41-year-old, tipped to be the next James Bond, said he hopes people will be mindful of how they treat historic sites.
Diana Gabaldon, the show’s writer, has urged fans to “tread lightly” at heritage sites after learning that stones had been taken from the Culloden battlefield.
Heughan’s plea comes ahead of his appearance at Aye Write book festival in Glasgow with co-star Graham McTavish to discuss Clanlands – a book based on their road trip around Scotland.
Speaking to The Times before the festival from May 14 and 23, Heughan said: “Hopefully, reading our book or other books, people will understand the history of what happened and treat historic sites with the respect they are due.”
McTavish said: “I certainly don’t agree with people taking souvenirs. These places are to be shared by everybody and if you start dismantling them for your own selfish gain, then that’s not helping anybody at all.”
Heughan has gathered a global following his portrayal of Highland warrior Jamie Fraser in the fantasy drama which charts the adventures of Claire Randall, a former Second World War combat nurse played by Irish actress Caitriona Balfe.
Randall is on a second honeymoon to Scotland with her husband Frank in 1945 when she is mysteriously transported back in time to 1743. It is here, on the cusp of the Jacobite rising, that she meets the dashing Fraser.
Heughan’s teenage years were spent in Edinburgh before he went on to study at the Royal Scottish Academy of Music and Drama in Glasgow.
Early roles include parts in River City, Midsomer Murders and the BBC soap opera Doctors, before Heughan landed his big break in Outlander in 2013.
His part in David Greig's Outlying Islands in 2002 saw him nominated for a Laurence Olivier Award as most promising new performer.
The star, from New Galloway, Kirkcudbrightshire, has thrown his support behind plans for film studios in Scotland, arguing that previous opportunities had been missed because of a lack of facilities.
“There are big, big productions coming to Scotland and so the more we can encourage them, the better,” he said.
While he has admitted he would "jump at the chance” to step into the shoes of Daniel Craig, who has played 007 since 2006, Heughan has played down Bond rumours.
Recently he revealed his ambitions to make a theatre comeback, after being cast in action movies for years.
Heughan said: “I'd love to go back to theatre. I have been talking to various people, before the pandemic.”
The actor has also revealed being asked what was under his kilt has become “rather boring”.
“I’m still trying to think of a good answer,” he said.
The Outlander stars will speak about Clanlands on May 16. The talk is part of a programme of literary events that involves 140 authors.