The highly-anticipated period movie, starring Leonardo DiCaprio, Brad Pitt, and Margot Robbie, was a late addition to the official competition line-up for the annual event in France, where it will be screened for the first time on Tuesday, May 21.
As he prepares for the premiere, Tarantino has issued a personal plea to attendees via social media, asking them to keep all plot twists under wraps, so fans around the world can enjoy the story unfold for themselves.
In the typed message, he wrote: "I love Cinema. You love Cinema. It's the journey of discovering a story for the first time.
"I'm thrilled to be here in Cannes to share 'Once Upon A Time... In Hollywood' with the festival audience. The cast and crew have worked so hard to create something original, and I only ask that everyone avoids revealing anything that would prevent later audiences from experiencing the film in the same way. Thank you, Quentin".
The note, posted on Instagram and Twitter, is captioned with the hashtag, "#NoSpoilersInHollywood".
The film is set in the late 1960s and revolves around a washed-up western star, played by DiCaprio, who lives next door to tragic actress Sharon Tate - one of the victims murdered by members of Charles Manson's cult The Family.
Pitt plays the longtime stunt double of DiCaprio's character, Rick Dalton, while Robbie portrays Tate.
Al Pacino, Damian Lewis, Kurt Russell, Dakota Fanning, Timothy Olyphant, Margaret Qualley, Tim Roth, and the late Luke Perry also feature in Tarantino's latest movie, which is set for release in late July.