Christian Loader, Dan Cook, Neil Spence and Jon Pritchard have all felt the chop and will be replaced by Colin Noon, Glen Kenworthy, Russell Earnshaw and Joe Ewens respectively.
The Titans are determined to lift themselves up after their dissapointing start to the season and they are well aware how important a home victory is – not wanting to follow the example of Leeds and Newcastle, who both lost at home last week.
"Quins will produce a different type of threat and after their excellent win against Wasps, confidence will be high," said CEO Jim Kilfoyle.
"But, at the same time, it won't be easy for them to come to Millmoor and they'll have to show that they've put their troubles on the road firmly behind them.
"This game is an immensely significant day for Rotherham Titans, your home form is crucial to survival and your first home match can influence the mood in any camp."
Rotherham Titans: 15 John Benson, 14 Anthony Elliot, 13 Joe Ewens, 12 Peter Jorgensen, 11 Michael Wood, 10 Jason Strange, 9 Jacob Rauluni, 8 Geraint Lewis, 7 Russel Earnshaw, 6 Leon Greeff, 5 Glen Kenworthy, 4 Luke Gross, 3 Colin Noon, 2 Chris Johnson (captain), 1 Nick Lloyd.Replacements: 16 Peter Smyth, 17 Chris Loader, 18 Dan Cook, 19 James Cockle, 20 C Short, 21 Charlie Harrison, 22 Jason Keyter.
Kick-off: 14.45 BST (13.45 GMT)