The Arsenal playmaker has warned his team to be wary of the Copa America winners, while stating he will be at Spain's disposal when called upon
The European and world champions will face Oscar Tabarez's men in the Group B opener as favourites, but Cazorla is anticipating the potential pitfalls awaiting his side.
"For us, the most important match is the Uruguay one. They're a difficult team to beat and are very competitive," the 28-year-old told Marca. "We need to be well prepared to face up to them.
"They don't just have [Edinson] Cavani and Luis Suarez - they also have a Golden Boot winner in [Diego] Forlan. It's a team that poses a great threat up front.
"The game will be completely different from the one we played a few months ago [Spain won 3-1]. This game is much more important than a friendly."
The Arsenal star came off the bench in the victory against Ireland last Wednesday, providing an assist for Juan Mata, and Cazorla has reiterated that he has no qualms accepting his role as a substitute.
"I consider myself lucky just to be part of this group. It would be great to get some time on the pitch, but I know how difficult it is to get into this team," he added.
"You need to make a contribution, hopefully by playing, but otherwise I will make my contribution during each training session, supporting my team-mates.
"Not playing wouldn't be a disappointment for me."
Uruguay warmed up for the blockbuster with a 1-0 win against Venezuela last Wednesday.