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The working titles of this film were It Happened One Night and Night Bus. According to a September 1954 Los Angeles Times news item, Van Johnson and Constance Towers were considered for the starring roles. By November 1954, a Los Angeles Times news item announced that Robert Mitchum was to star with June Allyson. Although a Hollywood Reporter production chart places Irving Bacon in the cast, he was not in the released film. Producer-director Dick Powell was married to Allyson. This was the only film in which Powell directed Allyson.
You Can't Run Away from It was based on Samuel Hopkins Adams' short story "Night Bus," which also served as the basis for the 1934 Columbia film It Happened One Night, which starred Clark Gable and Claudette Colbert and was directed by Frank Capra. The 1956 film took place on a Texas to California trip, rather than the Florida to New York setting of the 1934 film. Robert Riskin, who wrote the screenplay for It Happened One Night is credited along with Claude Binyon for the screenplay of You Can't Run Away from It. Although many films purport to be remakes of It Happened One Night, You Can't Run Away from It is the only true remake in that it is the only film based on the same source as It Happened One Night.