The Vodacom URC encounter at Cardiff Arms Park, which kicks off at 20h35 SA time on Saturday, will mark Malherbe's 124th appearance for the DHL Stormers, to go past the great Schalk Burger.
He will run out alongside Steven Kitshoff, who reaches 122 DHL Stormers caps, and is poised to move past Burger in the near future.
Malherbe - who also made his Test debut in Cardiff, in 2013, and is currently on 54 Bok caps - and Kitshoff start either side of fellow Springbok hooker Joseph Dweba, with Kwenzo Blose, JJ Kotze and Brok Harris backing them up from the replacements bench.
DHL Stormers head coach John Dobson said that Malherbe's achievement cannot be taken for granted.
"What Frans has achieved at the age of just 31 is incredible, if you think about some of the players who represented this team before him," said Dobson.
"He is a great example of a top team man and just his presence in the squad this week has given us a lift."
Adre Smith starts alongside Marvin Orie in the second row, with Ernst van Rhyn taking the captaincy in a start at blindside flank and Nama Xaba and Hacjivah Dayimani rounding out the loose trio.
There are just two changes to the backline, with scrumhalf Godlen Masimla and wing Suleiman Hartzenberg coming into the starting line-up.
Paul de Wet and Sacha Mngomezulu provide cover from a replacements bench which also features Ben-Jason Dixon, Willie Engelbrecht and Junior Pokomela, who are sure to make an impact in the second half.
Dobson said that it will take big effort to get the result in Cardiff: "We are looking forward to seeing how some of our combinations develop and the way the team responds at what is a renowned rugby venue against a home team with some momentum."
DHL Stormers: 15 Clayton Blommetjies, 14 Suleiman Hartzenberg, 13 Alapati Leuia, 12 Dan du Plessis, 11 Leolin Zas, 10 Manie Libbok, 9 Godlen Masimla, 8 Hacjivah Dayimani, 7 Ernst van Rhyn (captain), 6 Nama Xaba, 5 Marvin Orie, 4 Adre Smith, 3 Frans Malherbe, 2 Joseph Dweba, 1 Steven Kitshoff. Replacements: 16 JJ Kotze, 17 Kwenzo Blose, 18 Brok Harris, 19 Ben-Jason Dixon, 20 Willie Engelbrecht, 21 Junior Pokomela, 22 Paul de Wet, 23 Sacha Mngomezulu.