NASA has implemented new radiation quality factors (QFs) for projecting cancer risks from space radiation exposures to astronauts. The NASA QFs are based on particle track structure concepts with parameters derived from available radiobiology data, and NASA introduces distinct QFs for solid cancer and leukaemia risk estimates. The NASA model was reviewed by the US National Research Council and approved for use by NASA for risk assessment for International Space Station missions and trade studies of future exploration missions to Mars and other destinations. A key feature of the NASA QFs is to represent the uncertainty in the QF assessments and evaluate the importance of the QF uncertainty to overall uncertainties in cancer risk projections. In this article, the biophysical basis for the probability distribution functions representing QF uncertainties was reviewed, and approaches needed to reduce uncertainties were discussed.