Franklin is best known for her work on the X-ray diffraction images of DNA while at King's College London, particularly Photo 51, taken by her student Raymond Gosling, which led to the discovery of the DNA double helix for which Francis Crick, James Watson, and Maurice Wilkins shared the Nobel Prize in Physiology or Medicine in 1962. Watson suggested that Franklin would have ideally been awarded a Nobel Prize in Chemistry, along with Wilkins but it was not possible because the pre-1974 rule dictated that a Nobel prize could not be awarded posthumously unless the nomination had been made for a then-alive candidate before Feb 1st of the award year and Franklin passed away a few years before 1962 when the discovery of the structure of DNA was recognized by the Nobel committee.

Working under John Desmond Bernal, Franklin led pioneering work at Birkbeck on the molecular structures of viruses. On the day before she was to unveil the structure of tobacco mosaic virus at an international fair in Brussels, Franklin died of ovarian cancer at the age of 37 in 1958. Her team member Aaron Klug continued her research, winning the Nobel Prize in Chemistry in 1982.