Audrey Hepburn was first offered the role of Anne Frank, and Otto Frank was among those who nominated her. She refused it for three reasons. Firstly, she had decided to accept the role in A Flor Que Não Morreu (1959). Secondly, she had lived in occupied The Netherlands during the war and had seen the Nazis carry out street executions and watched as they herded Jews onto boxcars to carry them to concentration camps. She knew that making the film would bring back memories that were far too painful for her. However, thirdly, she was 30 and felt that she was too old to play a teenage character convincingly on screen.
Shelley Winters donated the Best Supporting Actress Academy Award she won for the role of Mrs. Van Daan to the Anne Frank Museum in Amsterdam, after promising Otto Frank that she would do so if she were to win the award. It remains on permanent display in the museum to this day.
Otto Frank and one of the men who had helped his family, Johannes Kleiman, were hired as technical advisers. Otto Frank worked closely with the production, met with Diane Baker and Millie Perkins, and approved their casting as his late daughters Margot Frank and Anne Frank. However, he never could bring himself to watch the play or film.
George Stevens chose to film in black and white as he believed it would heighten the drama. He also deliberately shot some scenes in near darkness, forcing the viewer to really concentrate on the details.
Shelley Winters had to gain 25 pounds for the role of Mrs. Van Daan. She then had to lose 15 of it as the movie progressed.