Marc Wilmots' men face the United States in the round of 16 on Tuesday and are favourites despite being without Thomas Vermaelen, Anthony Vanden Borre and possibly Vincent Kompany due to injury, while Steven Defour will miss the match through suspension.
Witsel, 25, expects Belgium to reach the last eight and said it would be a major disappointment if they failed to do so.
"I think it's clear. If we fail to qualify for the quarter-finals, it will be a failure for us because we have a great team with great players and we have the quality to reach the quarter-finals," he told a news conference.
"If we don't go through, we will be very disappointed."
Attacking midfielder Eden Hazard has been criticised for his performances at Brazil so far, with even Wilmots demanding more of the Chelsea star.
Witsel still believes Hazard can make the difference, starting with the clash against the USA in Salvador.
"We all trust in Eden. Everyone knows his great qualities," Witsel said.
"He wants to make a difference all the time and I'm sure we will see the great Eden Hazard. He can still be decisive."
Witsel said the midfield battle would be critical and he wants his team to control possession.
"It will be a tough game, which will probably be played mentally. Physically, it will be very tough," he said.
"I think once again, it will be decided in midfield. It is up to us to control the game, to have possession of the ball. I think we have the players and the quality to do so.
"We will give everything and try to lead the way."
