Kekilli’s most recognizable role to international audiences is , a prostitute and later mistress to Tyrion Lannister, appearing in the first four seasons of Game of Thrones (2011–2014).

Kekilli’s rise to prominence began with a "fearless" debut that remains a landmark in modern German film. (Gegen die Wand, 2004): Directed by Fatih Akin, this film earned Kekilli her first Lola Award

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Kekilli’s portrayal of Shae was distinct. In a show often criticized for its gratuitous use of female nudity, Kekilli brought a grounded wit and genuine vulnerability to the role. She elevated Shae from a plot device to a character with agency. Her chemistry with Peter Dinklage (Tyrion Lannister) provided the show with some of its most intimate, human moments.