Before becoming a professional writer, literary translator and interpreter, Guilloux worked in various trades, including journalism. He was well known for his fluency in the English language. He married in 1924, and published La Maison du Peuple in 1927.
The success of the book led to a long series of novels on socially committed themes, usually based in his native Brittany. His masterpiece Le Sang Noir was notable for its departure from his earlier, more staightforwardly socialist literature, since it contains elements of what was later associated with an existentialist or absurdist vision. It centres on the suicidal thoughts of the anti-hero, Cripure, who feels overwhelming disgust at humanity in the destructive circumstances of militarism during World War I.
Contrasted with the figure of Cripure is the nominal hero, Lucien, who aspires to work for a better future. But the grotesque and self-excoriating visions of Cripure are repeatedly portrayed as more powerful and compelling than Lucien's idealism. The book was translated into English under the title Bitter Victory.
Le Pain des Rêves (Bread of Dreams), which he wrote during the Occupation, won the Prix du roman populiste in 1942. After the liberation of France, Guilloux worked as an interpreter for the American Army of occupation. In "OK Joe!" he explored racial inequalities and injustice in the segregated American army of the time. Guilloux's experiences at this time are described by Alice Kaplan in her 2006 book The Interpreter.
His 1949 novel Le Jeu de Patience (Game of Patience) won the Prix Renaudot. It has been described as his most experimental work, "an intricate text demanding patient reconstitution by the reader. Micro- and macro-history collide: the horrors of war, and anarchist and Popular Front politics or right-wing coups, impinge violently on private dramas. It is a haunted kaleidoscope, often hallucinatory."
Guilloux was also a translator of a number of books, including the novel 'Home to Harlem' written by black American author Claude McKay, published in 1932 under the title Ghetto Noir. He also translated John Steinbeck, Margaret Kennedy, and Robert Didier, and some of the Hornblower series of novels by C.S. Forester. Towards the end of his life he created scripts for television adaptations of literary classics.
Louis Guilloux was friendly with many notable writers. He knew the philosopher Jean Grenier from his teenage years, and was close to Albert Camus. He was also friends with André Malraux and Jean Guéhenno. Camus praised his work highly, and compared his story Compagnons (Companions) to Leo Tolstoy's 'The Death of Ivan Ilyich.'
eBook Le Jeu de patience, tome 1