Hands is the daughter of British director Terry Hands and French actress Ludmila Mikaël, and the granddaughter of painter Pierre Dmitrienko. She studied acting at the Cours Florent and the CNSAD in France, and the London Academy of Music and Dramatic Art in England. In 1999, she made her stage debut in Le bel air de Londres by Dion Boucicault, and was nominated for a Molière Award. Her first film was Andrzej Zulawski's La Fidélité (2000), followed by The Barbarian Invasions (2003). She then appeared in Les Âmes grises (2005), for which she was nominated for the César Award for Most Promising Actress, and Ne le dis à personne (Tell No One) (2006).
Her most notable performance to date was in the title role of Lady Chatterley (2006), an adaptation of John Thomas and Lady Jane by D. H. Lawrence. Hands won the 2007 César Award for Best Actress for her performance.
In 2006, Hands became a company member of the Comédie-Française.