Wales Under-20 ace Smith, who has made 14 appearances for Cardiff Blues but never in European action, is called into the starting line-up for the Challenge Cup encounter as Head Coach Danny Wilson makes five changes to the side that defeated the French side last week.
Scrum half Tavis Knoyle is the other change in the back division where he will combine forces with fly half Jarrod Evans.
Prop Gethin Jenkins returns to captain the team in the front row while lock Lou Reed is called up to the second row to partner Jarrad Hoeata.
The final change is a recall for fit-again Italian international Number Eight Manoa Vosawai, who slots in the back row alongside Josh Navidi and Macauley Cook.
USA international Blaine Scully is named among the replacements alongside utility back Tom Isaacs and talented young prop Dillon Lewis.
Sam Warburton, Cory Allen, Gareth Anscombe, Ellis Jenkins, Gavin Evans and Dan Fish are among those ruled out through injury while Matthew Rees continues to serve a suspension.
Head Coach Wilson: “To progress from the group it is a game we ultimately need to look to win.
“If we can beat them away it probably comes down to a winner takes all against Harlequins in January, but we are fully aware of the task ahead of us now in France.
“To go and beat the squad that Montpellier have at their place will be a big ask. But we have made good strides in recent weeks to get a far better performance.
“Over the last three games we have taken steps in the right direction. This is another huge challenge before we come back to two derby games so the games are coming thick and fast.
“They are tough games for us at the moment. But if we can keep players fit and be competitive then we can challenge for results.”
Cardiff Blues: 15 Rhys Patchell, 14 Alex Cuthbert, 13 Garyn Smith, 12 Rey Lee-Lo, 11 Tom James, 10 Jarrod Evans, 9 Tavis Knoyle; 1 Gethin Jenkins (c), 2 Kristian Dacey, 3 Taufa’ao Filise, 4 Jarrad Hoeata, 5 Lou Reed, 6 Macauley Cook, 7 Josh Navidi, 8 Manoa Vosawai
Replacements: 16 Ethan Lewis, 17 Sam Hobbs, 18 Dillon Lewis, 19 James Down, 20 Josh Turnbull, 21 Lloyd Williams, 22 Tom Isaacs, 23 Blaine Scully