She has published numerous novels, essays and short stories, which have been translated into 28 languages and are published by Penguin Random House and in German by Knaus Verlag. Xiaolu Guo is also an award-winning director. She has taught film directing, literature, and creative writing at Harvard, Columbia, Zurich, and Bern Universities, among others, and was a fellow at the DAAD's Berlin Artists-in-Residence Program in 2012. Retrospectives of her cinematic work have been shown at the Swiss Film Archive (2011), the Greek Film Archive (2018), and London's Whitechapel Gallery (2019).

In her work, Guo explores complex interrelationships of migration, foreignness and memory, as well as transnationality and translation in a variety of ways. She became known to a wider audience through her award-winning film How Is Your Fish Today (2006). Influenced by Alain Robbe-Grillet, the docu-drama metafictionally tells the story of an unsuccessful author and his protagonist, whose lives intertwine in mysterious ways. Guo then achieved international success with her novel A Concise Chinese-English Dictionary for Lovers (2008), which was translated into 26 languages and shortlisted for the Orange Prize for Fiction. Inspired by Roland Barthes and written in Broken English, the novel is about a young Chinese woman, Zhuang, who comes to London to learn English, observes the unfamiliar daily life in the foreign city, and encounters love in the cinema. The following year saw the release of the film She, a Chinese, with which Guo won the Golden Leopard at the Locarno Film Festival in 2009. The film depicts monotony, hope of departure, and violence in the life of Li Mei, a young Chinese woman who makes her way from her native Chinese village to the larger city of Chongqing to London, reflecting on the challenges of cultural (re-)ruptures between East and West. In 2017, Once Upon a Time in the East (US edition: Nine Continents) was published. In this autobiographical text, Guo recounts her childhood spent with her grandparents in an eastern Chinese fishing village, her time in Beijing, a city of vibrant contradictions and rapid change, and her move to London, where her daughter is born. The work paints a fascinating portrait of China in the 1980s and 1990s, circling the familiar strangeness of a life caught between East and West. Guo received the National Book Critics Circle Award (2017) and placements on the RSL Ondaatje Ward, Costa Award, and Folio Prize shortlists for it. Her most recent publication is the novel A Lover's Discourse (2020).