The back-line remains unchanged apart from Paddy Wallace dropping to the replacements bench to accommodate Humphreys.
Bryan Young starts at loosehead prop with Justin Fitzpatrick named on the bench.
Carlo Del Fava picked up an injury against Glasgow so Ryan Caldwell starts in the second row alongside Justin Harrison, who will be making his final appearance for Ulster before moving onto Bath.
Stephen Ferris returns from injury at blindside flanker with Matt McCullough making way and Kieron Dawson starting at openside.
Meanwhile, young wingers Roger Davies and Leigh Halfpenny will make their debuts for the Cardiff Blues in Belfast.
The Blues have already secured their position as top-placed Welsh team in the Magners League this season, and with a four-point cushion over Munster, a win against Ulster will cement their place as runners-up in the final league pecking order.
The Blues' line-up shows wholesale changes to the team that recorded a 39-11 win against Connacht in Galway last Friday.
Nicky Robinson, Xavier Rush, Scott Morgan, Maama Molitika and Taufa'ao Filise the only players to keep their starting places.
ULSTER: Mark Bartholomeusz; Tommy Bowe, Andrew Trimble, Rob Dewey, Simon Danielli; David Humphreys, Isaac Boss; Bryan Young, Rory Best (capt), Tom Court, Justin Harrison, Ryan Caldwell, Stephen Ferris, Kieron Dawson, Roger Wilson.
Replacements: Nigel Brady, Justin Fitzpatrick, Matt McCullough, Neil Best, Paul Marshall, Paddy Wallace, Mark McCrea.
CARDIFF BLUES: Nick Macleod; Roger Davies, Marc Stcherbina, Dafydd Hewitt, Leigh Halfpenny; Nicky Robinson, Richie Rees; Taufa'ao Filise, Gareth Williams, Gary Powell, Bradley Davies, Scott Morgan, Maama Molitika, Ben White, Xavier Rush (capt).
Replacements: John Yapp, Rhys Thomas, James Down, Mark Lewis, Rhys Shellard, Jason Spice, Dai Flanagan.
Referee: Andy Macpherson (Scotland)
Say What: Matt Williams (Ulster) - "David (Humphreys) is an iconic figure in Ulster and Irish rugby and I hope the people of Ulster turn up to say thank you for a remarkable career.
"For a number of players this will be there last game with Ulster, so Friday night is the perfect opportunity for the fans to say their goodbyes to some much loved players.