The Maroons veteran of 17 games is set to line up at right centre, where limiting Mitchell's left-side raids and impact will be crucial at the MCG in game two of the Origin series on June 26.
Mitchell last played for NSW in 2021, when he wreaked havoc at centre.
At that stage, Holmes was playing wing and fullback for Queensland before his positional switch to centre for North Queensland and at representative level.
"I've played alongside him (for Australia) so I know he is pretty dangerous when he attacks the line," Holmes said of the South Sydney star.
"It is a while since he has played in the Origin arena so we will try and get to him in ways that slow him up a bit.
"I have just got be in his face and make my tackles.
"In club footy when I play centre and he is fullback (for South Sydney) and he sweeps around the back you try and make decisions on him.
It has not been centre-on-centre because he hasn't really played centre when I have played it."
Mitchell has played fullback since joining the Rabbitohs in 2020.
Holmes said he expected Mitchell to adapt and handle the defensive aspect of the centre role.
Mitchell's aggression is well understood by the Maroons but they have no intention of making life easy for the Blues man.
"He is a classy player who will get back into the swing of things," Holmes said of Mitchell's Origin return.
"You have got to make more defensive reads at centre but he is such a big boy and is a good mover who can back himself to make those tackles.
"He is pretty aggressive so he will probably come out and look to jam Walshy (fullback Reece Walsh) and get into our back five early.
"We have to be wary of that and make him work a bit more than he does at Souths."
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