Kick-off at Emirates Airline Park is at 15h30 and the action will be live on SuperSport.
Apart from Smith's return, James Verity-Amm gets a start on the wing with Stravino Jacobs moving to the bench as the men from Pretoria continue exploiting its depth, with the aim to make it four wins on the trot in their Rainbow Cup campaign.
Vodacom Bulls Director of Rugby Jake White has made a number of changes upfront, with Springbok props Lizo Gqoboka and Trevor Nyakane earning starts in a direct swap with Gerhard Steenekamp and Mornay Smith.
Elrigh Louw returns to the blindside flank position, resuming his successful combination with Springbok loose forwards Marco van Staden and captain Duane Vermeulen.
Springbok loose forward Nizaam Carr and utility back Clinton Swart shift up to the bench where they will undoubtedly add a boost in the second half.
"The more we are successful on the pitch, the bigger the target on our back gets," said White.
"The Lions will not be happy with their returns over the first three matches and they will come out hunting this weekend. We need to be effective in playing our brand of rugby and keeping our momentum going."
Vodacom Bulls: 15 David Kriel, 14 Madosh Tambwe, 13 Marco Jansen van Vuren, 12 Cornal Hendricks, 11 James Verity-Amm, 10 Chris Smith, 9 Embrose Papier, 8 Duane Vermeulen (captain), 7 Elrigh Louw, 6 Marco van Staden, 5 Ruan Nortje, 4 Walt Steenkamp, 3 Trevor Nyakane, 2 Johan Grobbelaar, 1 Lizo Gqoboka. Replacements: 16 Schalk Erasmus, 17 Gerhard Steenekamp, 18 Mornay Smith, 19 Janko Swanepoel, 20 Nizaam Carr, 21 Zak Burger, 22 Clinton Swart, 23 Stravino Jacobs.
Date: Saturday 22 May
Venue: Emirates Airline Park, Johannesburg
Referee: AJ Jacobs
Assistant Referees: Aimee Barrett-Theron, Morne Ferreira
Television Match Official: Marius Jonker
TV: SuperSport Rugby and Grandstand channels