In 1964, following Cartan's advice, he began to work with Alexandre Grothendieck, collaborating with him on two volumes of the latter's Séminaire de Géométrie Algébrique du Bois Marie.

In May 1971, Illusie defended a state doctorate ((in French) Thèse d’État) entitled "Cotangent complex; application to the theory of deformations" at the University of Paris-Sud, in front of a jury composed of Alexander Grothendieck, Michel Demazure and Jean-Pierre Serre and presided by Henri Cartan.

The main results of the thesis are summarized in a paper in English (entitled "Cotangent complex and Deformations of torsors and group schemes") presented in Halifax, at Dalhousie University, in January 1971 as part of a colloquium on algebraic geometry.

[4] Illusie's construction of the cotangent complex generalizes that of Michel André[8] and Daniel Quillen[9] to morphisms of ringed topoi.

In Chapter VIII of the second volume of the thesis, Illusie introduces and studies derived de Rham complexes.