Natali's directing debut came in 1997, when he was approached to direct Cube (1997). The film became a success worldwide, especially in Japan and France, grossing $15 million in France, and breaking box office records for a Canadian film. At the 19th Genie Awards, the film received five nominations and also won the award for Best Canadian First Feature at the Toronto International Film Festival. After this success, Natali went on to direct Cypher (2002) and Nothing (2003).
^Riser, Troy (21 October 2005). "Interview: Vincenzo Natali: Turtles All The Way Down". the-trades.com. The Trades. Retrieved 10 April 2011. "There really weren't too many touchstones, literary or otherwise. Except Beckett. We do owe a small debt to the Theatre of the Absurd." "Yes. He's a huge influence. But we're very different kinds of directors."
^Stubbs, Phil (2005). "Vincenzo Natali on the making of Tideland". smart.co.uk. Dreams – The Terry Gilliam Fanzine. Retrieved 10 April 2011. "Yes I have a new film called Nothing - which is a title that causes endless confusion. It was just released in Canada a few months ago. If there is a single film that I've done that owes a real debt to Terry, that's it actually."
^Turek, Ryan (13 December 2010). "Exclusive: Vincenzo Natali Fills Us In On 388 Arletta Avenue". Shock Till You Drop. Retrieved 3 June 2011. "A week and a half out from the end of principal photography, executive producer Vincenzo Natali gave Shock Till You Drop a call to discuss the nature of 388 Arletta Avenue, a new thriller we learned about at the American Film Market this year that has attracted the cast Nick Stahl, Mia Kirshner and Devon Sawa."