Plisnier appeared as a heretic to the majority of his contemporaries, as the existence of God never ceased to be an active question for him; throughout his life, he experienced periods of profound atheism and of mystical crisis.

Mariages (1936; in English as Nothing to Chance, 1938) deals with the limitations of social conventions; the five-volume Meurtres (1939–41; "Murders") centres on an idealistic tragic hero, Noël Annequin, in his fight against hypocrisy.

A recurring theme in his works is the moral and psychological study of individuals in crisis, such as in L'Enfant aux stigmates (1931; "The Child With Stigmata"), which recalls the fatalism of Maurice Maeterlinck.

Plisnier also wrote poetry: his early poetical works, such as Prière aux mains coupées (1930; "Prayer with Severed Hands"), deal with his struggle to reconcile religion and politics, while Fertilité du désert (1933; ”Fertility of the Desert”) shows an influence of surrealism.

[2] In 1937, Plisnier won the Prix Goncourt for Faux passeports ("False Passports"; in English as Memoirs of a Secret Revolutionary, 1938), a collection of short stories denouncing Stalinism, in the same spirit as Arthur Koestler.