Sean Lamont switches to the wing with his younger brother sidelined after undergoing surgery on a leg fracture sustained in the 23-17 defeat against France on February 26.
There are three changes on the bench with Euan Murray, Ruaridh Jackson and Max Evans replacing Ed Kalman, Duncan Weir and De Luca respectively.
Scotland have lost all three matches in the tournament but coach Andy Robinson believes his side can surprise Ireland if they get their game right on the day.
"We did many good things in the game against France but we need to be better, especially in our accuracy and execution at breakdown, in order to beat Ireland," Robinson said in a Scottish Rugby statement.
"If we do the basic things well and are ruthless in contact then we can put ourselves in a position to defeat a very good Ireland team."
Scotland: 15-Stuart Hogg, 14-Lee Jones, 13-Nick De Luca, 12-Graeme Morrison, 11-Sean Lamont, 10-Greig Laidlaw, 9-Mike Blair, 8-David Denton, 7-Ross Rennie, 6-John Barclay, 5-Jim Hamilton, 4-Richie Gray, 3-Geoff Cross, 2-Ross Ford (captain), 1-Allan Jacobsen
Replacements: 16-Scott Lawson, 17-Euan Murray, 18-Alastair Kellock, 19-Richie Vernon, 20-Chris Cusiter, 21-Ruaridh Jackson, 22-Max Evans.
