The in-form Andrew Bishop moves out a place to outside centre to accommodate Henson's return while a groin injury to Jonathan Thomas means Filo Tiatia starts to form a formidable backrow alongside fellow Kiwi Marty Holah and skipper Ryan Jones who plays on the blindside flank.
Holley said: "Saturday's game is a huge fixture that will provide a real test of physical and mental strength, but it's an exciting challenge that we are all looking forward to.
"You can't fail to be excited about the prospect of challenging one of France's leading sides on their own patch, in front of a big crowd and in an electric atmosphere. Our players are the type who thrive on competing against the best in the world in front of big, passionate crowds and Perpignan certainly fit the bill.
"Our recent matches against the Blues and Munster were both hugely physical, and as such, have proved to be excellent preparation for this fixture. We welcome back six seasoned internationals into the starting 15, along with Jamie Nutbrown on the bench, whilst Tom Smith deservedly takes a place in the 22 after a fine performance last weekend.
"After reviewing the Munster match we have identified clear areas for improvement, and if we can hit the right performance marks in terms of what we've been working hard on this week then we will present a serious challenge to Perpignan."
Ospreys: L. Byrne; T. Bowe, A. Bishop, G. Henson, S. Williams; J. Hook, M. Phillips; P. James, R. Hibbard, A. Jones, I. Gough, A.W. Jones, R. Jones (capt), F. Tiatia, M. Holah. Reps: H. Bennett, C. Griffiths, L. Bateman, T. Smith, D. Biggar, J. Vaughton