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After qualifying as a doctor in 1983, Evans worked in medicine in Newcastle for four years before a brief period in stand-up, beginning with an ensemble review called "Wire Less Wireless" which played in some of the pubs in Newcastle. Evans joined BBC Radio where she was a producer of comedy programmes before migrating to television. She has produced and/or directed such shows as Father Ted (for which she won a BAFTA for best comedy), Room 101, The Kumars at No. 42, TV Heaven, Telly Hell, Crossing the Floor (for which she won an Emmy for best drama) and Have I Got News For You.
Evans has written four novels for adults: Spencer's List, Odd One Out, Their Finest Hour and a Half (now filmed as Their Finest) and Crooked Heart, the last two both long-listed for the Baileys Women's Prize for Fiction. The novel Old Baggage was published in 2018.
For children, she has written Small Change For Stuart, shortlisted for the 2011 Costa Award for Children's fiction, the 2012 Carnegie Medal, and the 2012 Branford Boase Award. Small Change for Stuart was published in the United States as Horten's Miraculous Mechanisms, and the sequel, Big Change for Stuart (Horten's Incredible Illusions in the U.S.) was published in 2012. Another book for children, Wed Wabbit, was published in 2017 and shortlisted for the 2017 Costa Book Awards and the 2018 Carnegie Medal.
- Spencer's List (2003)
- Odd One Out (2005)
- Their Finest Hour & a Half (2009)
- Crooked Heart (2015)
- Old Baggage (2018)
- Small Change For Stuart (2011)
- Big Change For Stuart (2012)
- Wed Wabbit (2017)
- Evans, Lissa (29 December 2018). "Lissa Evans on Lichfield: 'I went into the library the day we moved and never really came out'" – via www.theguardian.com.
- Evans, Lissa (22 April 2017). "how my novel about film-making was turned into a film". The Guardian. Retrieved 22 April 2017.
- Fey, Suzi (14 June 2018). "Old Baggage by Lissa Evans review – suffrage and showdowns". The Guardian. Retrieved 29 December 2018.
- Smyth, Nicola (24 July 2011). "Children's Fiction: How to avoid being eaten, and other life lessons". The Independent. Retrieved 28 July 2011.