The former Celtic and Arsenal forward believes that Championship club Wednesday will win the game against League Two side Carlisle 3-0.
Nicholas has also backed Wednesday striker Jordan Rhodes to score the opening goal of the match.
The Scotland international is a proven goalscorer in the Championship, but the performances of the former Huddersfield Town and Middlesbrough striker so far this season have not been great.
The 27-year-old striker joined Wednesday on loan from Middlesbrough in January 2017 for the rest of the 2016-17 campaign and signed a permanent contract with the Owls in the summer of 2017 for a transfer fee reported by Gazette Live to be worth £10 million.
Nicholas wrote on Skysports.com: “This was my tip for a surprise in the last round, but Wednesday managed to get a replay despite failing to score yet again.
“Jos Luhukay will be looking to build on a positive result in the Steel City derby and I think he will play the strongest team to get a result.”
A footnote added: “Charlie predicts: 3-0 and Jordan Rhodes to score first.”