Llodra, buoyed by a home crowd in Montpellier, reeled off victory in straight sets, 6-3 7-6(4) against the second seed.
Llodra fired 13 aces and attacked throughout, eventually finishing with a total of 20 winners.
"My serve was good today and that helps on a quick surface like this," Llodra said. "There wasn't much in it, but I think I had more chances than him. I'm very happy to have won in straight sets."
Tipsarevic was effectively the top seed after Tomas Berdych withdrew before the tournament began.
There was more good news for French players as fourth seed Gilles Simon also reached the quarter-finals, beating Arnau Brugues-Davi 7-6(5) 6-2 to set-up an all-French showdown against Benoit Paire.
And in another all-French clash third seed Richard Gasquet won through to the last eight at Gael Monfils' expense.
6-Julien Benneteau (France) beat Victor Hanescu (Romania) 6-4 6-4
3-Richard Gasquet (France) beat Gael Monfils (France) 6-3 2-6 6-3
Michael Llodra (France) beat 2-Janko Tipsarevic (Serbia) 6-3 7-6(4)
Sergiy Stakhovsky (Ukraine) beat Tatsuma Ito (Japan) 6-7(4) 6-4 7-6(3)
4-Gilles Simon (France) beat Arnau Brugues (Spain) 7-6(5) 6-2
Jan Hajek (Czech Republic) beat 7-Viktor Troicki (Serbia) 6-0 4-2 (Troicki retired)
Ivan Dodig (Croatia) beat Ivo Karlovic (Croatia) 7-6(2) 6-7(2) 6-3
1-Marin Cilic (Croatia) beat Grega Zemlja (Slovenia) 6-2 6-3
Philipp Petzschner (Germany) beat Dino Marcan (Croatia) 6-3 6-4
Lukas Rosol (Czech Republic) beat Flavio Cipolla (Italy) 6-4 2-6 6-3
Blaz Kavcic (Slovenia) beat 6-Marcos Baghdatis (Cyprus) 3-6 7-6(2) 6-4
4-Jurgen Melzer (Austria) beat Somdev Devvarman (India) 1-6 7-6(5) 6-2
Robin Haase (Netherlands) beat 5-Martin Klizan (Slovakia) 6-2 4-6 6-4
ATP Vina del Mar
3-Jeremy Chardy (France) beat Christian Garin (Chile) 4-6 6-3 6-2
7-Daniel Gimeno-Traver (Spain) beat Albert Montanes (Spain) 6-4 6-4
6-Paolo Lorenzi (Italy) beat Tommy Robredo (Spain) 6-4 6-4
5-Albert Ramos (Spain) beat Filippo Volandri (Italy) 6-7(5) 6-3 7-5
Horacio Zeballos (Argentina) beat 4-Pablo Andujar (Spain) 6-3 6-3
- Sports & Recreation