The movie was written by Robert L. Joseph, Lupino, and her husband Collier Young, based on a story by blacklisted Out of the Past screenwriter Daniel Mainwaring (who did not receive screen credit). The film is based on the true story of psychopathic murderer Billy Cook.
It is regarded as the first mainstream film noir directed by a woman; in 1949 Norwegian director Edith Carlmar made the lesser known "Døden er et kjærtegn". The director of photography was RKO Pictures regular Nicholas Musuraca.
In 1998, The Hitch-Hiker was selected for preservation in the United States National Film Registry as being "culturally, historically or aesthetically significant."