The hosts have never won the Copa in its 99-year history but their impressive group stage performances have marked them out as favourites for glory on home soil.
Sampaoli, however, is wary of the defending champions due to their defensive ability and previous experience in high-profile matches.
"I believe the game for us is a final and it will be very complicated due to the opponents' characteristics," he said at a press conference.
"We will play against a team which knows how to play this kind of game. These are distinct matches with a mental factor. We cannot stand off. In this match Chile has to be on the front foot.
"We know what game we have to play, we know what we have to do collectively and we know that the opponents intend to neutralise this characteristic. We played them recently in Santiago and saw that despite completely dominating the game we ended up losing."
Uruguay earned a 1-1 draw with Paraguay in their final Group B game to confirm their place against Chile in the last eight through a José Giménez header, and Sampaoli admits La Celeste's strengths in the air could be a determining factor.
"[The aerial game of Uruguay] is a concern because they are specialists in that and because in certain moments of the match they know when to use it," he added.
"They have played against teams with more height than us and have always scored goals because they have good headers of the ball."
Chile come into the game in fine form having scored 10 goals in Group A's three matches and registering two victories as well as a draw.
With Argentina, Brazil and Colombia struggling for firepower, La Roja's coach believes his side have a unique opportunity to become top dogs on the continent.
"The group is doing well, we know their capabilities and the difficulties we could have in this game," he explained.
"I really feel the desire that Chile has and because of this I think we have a great chance of reaching the next phase. I am convinced the team will play a good match tomorrow, beyond the result.
"Tomorrow is another game where we have the possibility to qualify and each opportunity that Chile has is a step towards becoming one of the best teams in South America."
Sampaoli also called on Arsenal forward Alexis Sánchez to step up for the hosts following his first goal of the tournament in the 5-0 win against Bolivia.
"Alexis has to play an integral role for the function of the Chilean attack and has to impose himself with his skill and the form he is in."
Chile will play the winner of Peru v Bolivia should they progress to the last four.