Horstmann will lead out the hosts and his vice-captain will be centre Dale Rasmussen, who also plays his final game for the Warriors on home soil.
Head coach Richard Hill makes a total of five changes to the side that were beaten in the dying moments by Exeter Chiefs last time out.
A new-look back row sees Horstmann play at number eight, while flankers Sam Betty and Jake Abbott are recalled.
The other change in the pack comes in the front row where Ed Shervington joins forces with Matt Mullan and Tevita Taumoepeau.
Scrum-half Jonny Arr is the final change in a back division that will also see farewell home appearances for wing duo Miles Benjamin and Marcel Garvey who depart for Leicester and Castres respectively in the summer.
"We need a good result and have plenty of incentive to perform against a dangerous London Irish team who I fully expect to play without pressure and with real ambition," said Hill.
"It is sad to see a number of Warriors play their final game for the club at Sixways. I hope we can give them a good send-off with our fans given the chance to show them their respect while they get the chance to say goodbye."
Meanwhile, New Zealand international Bryn Evans will captain a London Irish team that shows four changes to the side that succumbed at home against Saracens last weekend.
Steven Shingler will start at fly-half in the one change to the back-line. In the pack, Max Lahiff and Leo Halavatau will join David Paice in the front-row, whilst England U20 international, David Sisi, comes into the back-row.
"We need to show the same effort and competitiveness that we have shown in recent weeks against Worcester tomorrow," said London Irish head coach Toby Booth.
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The entire All Blacks apparel line has been updated for 2013/14. Check out the New Zealand All Blacks polo.
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