American zoologist and embryologist, known for his discoveries concerning the fertilization of the egg (ovum) and the role of hormones in sex determination.

Lillie spent most of his career at the University of Chicago (1900–47), where he served as professor of embryology (1906–35), chairman of the zoology department (1910–31), and dean of the biological sciences division (1931–35). In his researches, Lillie found that the animal ovum is coated with a gelatinous substance composed of carbohydrate and protein, which he termed fertilizin. Its specific interaction with a substance surrounding sperm cells, called antifertilizin, causes the sperm to adhere to and penetrate the egg. The process is thought to ensure fertilization of the ovum only by sperm of its own species.

Lillie also demonstrated that bovine “freemartinism” is a classic example of hormonal intersexuality in which a male fetus influences the development of its female twin. Cattle twins may consist of two males, two females, or a male and a “freemartin,” an apparent female possessing a male's internal reproductive system. Knowing that sex hormones flow freely between fetal cattle twins, Lillie concluded that the freemartin is a genetic female masculinized by androgenic hormones from the male.

Throughout much of his life, he was associated with the Marine Biological Laboratory, Woods Hole, Mass., serving as its director (1908–26) and president of the corporation and board of trustees (1926–42). He was the founder and first president of the Woods Hole Oceanographic Institution (1930–39). His books include Development of the Chick (1908) and Problems of Fertilization (1919).