The sign of the cross is a ritual hand motion used by some Christians.

Sign of the Cross may also refer to:

• The Sign of the Cross (play), an 1895 play by Wilson Barrett
• The Sign of the Cross (1914 film), an American film directed by Frederick A. Thomson, based on Barrett's play
• The Sign of the Cross (1932 film), an American film directed by Cecil B. DeMille, based on Barrett's play
• The Sign of the Cross (book), 1994 book by Colm Tóibín
• Sign of the Cross (novel), 2006 novel by Chris Kuzneski
• Sign of the Cross, an album by Terveet Kädet
• "Sign of the Cross", a song by Iron Maiden on their album The X Factor
• "Sign of the Cross", a song by Avantasia on their album The Metal Opera
• "Sign on the Cross", a song by Bob Dylan on the album The Bootleg Series Vol. 11: The Basement Tapes Complete