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Lyon "are a strong team physically, but it's our turn to play at home," the Portuguese winger told a news conference.
"I was amazed by the fans on Saturday and I must thank them for their support. I hope we see the same kind of atmosphere on Wednesday because they will play a crucial role in our success. The stadium will be great to see so full and the players are ready."
Real lost 1-0 at Lyon in their last-16 first-leg match on February 16, and now have it all to do on Wednesday at the Santiago Bernabeu stadium - where this year's Champions League final will be played.
"Wednesday's match is do-or-die. We are playing very good football and we have proven that we are the strongest team in La Liga," said Ronaldo.
On Saturday, Real battled back from 2-0 down to beat Sevilla 3-2 and reclaim top spot in the Spanish first division.
Manuel Pellegrini's side are under pressure to bring the Champions League trophy back to Madrid after spending vast sums on big signings such as Ronaldo - the world's most expensive player - Brazil's Kaka and France's Karim Benzema.
The Spanish giants have fallen at the last-16 stage in the past five seasons and have not won Europe's most-coveted trophy since 2002 when they beat Germany's Bayer Leverkusen 2-1 in Glasgow.
On Wednesday, they will be without Benzema, who misses the match against his old club with a groin strain, as well as midfielder Xabi Alonso and left-back Marcelo through suspension.
"Everyone knows how bad this club wants to win the Champions League," said Ronaldo.
"It has nine titles and wants ten, and this year the final is being played here. I am sure we can turn this tie around... We have to prove to Lyon that we own the Bernabeu."
Real's French midfielder Lassana Diarra said an early goal is essential.
"We must start the match strongly, and above all watch out for their counter-attacks so as not concede a goal," he said.
