Director Fede Alvarez sought out the special effects crew from Aliens (1986) to work on the creatures. Physical sets, practical creatures, and miniatures were used wherever possible to help ground later VFX work.
The film's production design draws not only on the previous films in the series, but also the Alien: Isolation (2014) video game, including the "Emergency" communication stations which served as save points in the game. Fede Alvarez played the game around the time Don't Breathe (2016) was released, and later said, "I was playing, and realizing how terrifying Alien could be if you take it back to that tone."
Cailee Spaeny said this film takes place between Alien (1979) and Aliens (1986). It takes place in the year 2142, exactly 20 years after Alien (situated in 2122) and 37 years before Aliens (2179).
An early scene has a 'Drinking Bird' toy on the table. A similar toy featured in the original Alien (1979), and again in Alien³ (1992).
Director Fede Alvarez used a remote control soundboard connected to the loudspeakers around the set to spook the cast during shooting. It contained various sounds of xenomorphs and alarms.