The Czech side would go through regardless if Hapoel Kiryat Shmona and Athletic Bilbao were to draw when their postponed fixture is played.
Lyon are the only team in the competition with a 100 per cent record after four matches and they need one point to be sure of finishing top of the group, having already booked a place in the round of 32.
Sparta coach Vitezslav Lavieka said: "The point (we need) is both very near and very far. We will go into the match with the same determination with which we have gone into any of our previous home matches in the Europa League. We want to delight the fans and get the point."
Sparta's chances of sealing their qualification look to have improved after Lyon manager Remi Garde decided to rest a handful of senior players for the trip to the Czech Republic.
Milan Bisevac, Steed Malbranque, Arnold Mvuemba, Bafetimbi Gomis and Alexandre Lacazette have all remained in France, with Garde ready to field a youthful side in Prague.
Lavieka does not believe that will necessarily be a big benefit for his side, though, saying: "Lyon are a top European team who have a large squad and players who can replace members of the starting line-up, and they will certainly want to give a good performance."
Lyon are the leading scorers in the competition and opened their account with a 2-1 victory over Sparta in the opening round of matches.
However, Sparta are unbeaten in their last 10 European home matches and they have scored at least twice in each of them this season, so the French side will be wary of the threat posed by their opponents.