Former Ireland star Humphreys has been plagued with injuries this season but is back for his finale in Belfast.
"I am delighted to be playing on Friday night at Ravenhill, it's great to get a final opportunity to play for Ulster," he said.
"With the injuries I've suffered this season I didn't think it would happen. I'm really looking forward to running out one last time."
Ulster coach Matt Williams said: "I hope the people of Ulster turn up to say thank you for a remarkable career."
Paddy Wallace drops to the bench to accommodate Humphreys in the only change to the backline.
Bryan Young starts at loose head 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.
Stephen Ferris returns from injury to take his place as blind-side flanker with Matt McCullough dropping to be bench and Kieron Dawson starting at open-side.
Friday will also be a farewell to Ulster names Mark Bartholomeusz, Harrison, Neil Best, Tommy Bowe, Kieran Campbell and Roger Wilson, who leave the team after the game.
Williams is hoping that his side can finish a disappointing season on a high.
"Cardiff are the power house of Welsh rugby, European Cup quarter-finalists and fighting for second place in the Magners they will be a handful.
"A win this Friday would be a great send off for our players who are going to pastures new next season and would put the team on a real positive footing for next season."
Ulster are unbeaten in the league against Welsh sides at Ravenhill since November 2005 and the Blues have lost all their previous five matches there.
We are all hands to the pump at the minute with the Wales call-ups and also with injuries, so we are down to what we have got left
David Young
But the Cardiff region have won their last four league games in a row and five of their last six against Irish sides.
The Blues line up shows wholesale changes to the team that recorded a bonus point win against Connacht in Galway last Friday with Nick Robinson, Xavier Rush, Scott Morgan, Maama Molitika and Taufa'ao Filise the players keeping their starting berths.
Blues director of rugby David Young said: "The margin of the win was pleasing last week, and the boys were disappointed to let in a last minute try.
"Overall this season has been a big step forward for us. We won two out of three in the EDF, reached the quarter-finals of the Heineken Cup and are the best are the best-placed Welsh region in the Magners League.
"We've already started to look at areas where we can improve.
"We are all hands to the pump at the minute with the Wales call-ups and also with injuries, so we are down to what we have got left.
"We haven't trained much this week either because of our lack of numbers. However, it's nice to see two youngsters coming in on the wing.
"They have both played well for Cardiff this season and deserve their chance."
Ulster: M Bartholomeusz; T Bowe, A Trimble, R Dewey, S Danielli; D Humphreys, I Boss; B Young, R Best (capt), T Court, J Harrison, R Caldwell, S Ferris, K Dawson, R Wilson. Replacements: N Brady, J Fitzpatrick, M McCullough, N Best, P Marshall, P Wallace, M McCrea.
Blues: N Macleod; R Davies, M Stcherbina, D Hewitt, L Halfpenny; N Robinson, R Rees; G Powell, G Williams, T Filise, B Davies, S Morgan, B White, M Molitika, Xavier Rush (c).
Replacements: J Yapp, T R Thomas, J Down, M Lewis, R Shellard, J Spice, D Flanagan.
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