Rosalind Franklin joined the scientists at the Medical Research Unit, King's College, when John Randall recruited her to work on the structure of DNA. DNA (deoxyribonucleic acid) was originally discovered in 1898 by Johann Miescher, and it was known that it was a key to genetics. But it was not until the middle of the 20th century when scientific methods had developed to where the actual structure of the molecule could be discovered, and Rosalind Franklin's work was key to that methodology.

Rosalind Franklin worked on the DNA molecule from 1951 until 1953. Using x-ray crystallography she took photographs of the B version of the molecule. A co-worker with whom Franklin did not have a good working relationship, Maurice H. F. Wilkins, Wilkins showed Franklin's photographs of DNA to James Watson, without permission of Franklin. Watson and his research partner, Francis Crick, were working independently on the structure of DNA, and Watson realized that these photographs were the scientific evidence they needed to prove that the DNA molecule was a double-stranded helix.

While Watson, in his account of the discovery of the structure of DNA, largely dismissed Franklin's role in the discovery, Crick later admitted that Franklin had been "only two steps away" from the solution, herself.

Randall had decided that the lab would not work with DNA, and so by the time her paper was published, she had moved on to Birkbeck College and the study of the structure of the tobacco mosaic virus, and she showed the helix structure of the virus' RNA. She worked at Birkbeck for for John Desmond Bernal and with Aaron Klug, whose 1982 Nobel Prize was based in part on his work with Franklin.

Watson, Crick, and Wilkins were awarded the Nobel Prize in physiology and medicine in 1962, four years after Franklin died. The Nobel Prize rules limit the number of persons for any award to three, and also limit the award to those who are still alive, so Franklin was not eligible for the Nobel. Nevertheless, many have thought that she deserved explicit mention in the award, and that her key role in confirming the structure of DNA was overlooked because of her early death and the attitudes of the scientists of the time towards women scientists.

Watson's book recounting his role in the discovery of DNA displays his dismissive attitude towards "Rosy." Crick's description of Franklin's role was less negative than Watson's, and Wilkins mentioned Franklin when he accepted the Nobel. Anne Sayre wrote a biography of Rosalind Franklin, responding to the lack of credit given to her and the descriptions of Franklin by Watson and others. The wife of another scientist at the laboratory, herself a friend of Franklin, Sayre describes the clash of personalities and the sexism that had faced Franklin in her work. A. Klug used Franklin's notebooks to show how close she had come to independently discovering the structure of DNA.

In 2004, Finch University of Health Sciences/The Chicago Medical School changed its name to the Rosalind Franklin University of Medicine and Science, to honor Franklin's role in science and medicine.