Progress in cancer epidemiology and prevention has been a key determinant of the fall in cancer mortality in Europe. Using mortality and population figures from the WHO and Eurostat databases, we estimated the number of averted cancer deaths in the EU27 over the period 1989–2021, for both sexes, for all cancers, and nine major cancer sites. We also computed the avoided deaths for all cancers in five major European countries and the UK. We estimated a total of 4 958 000 (3 339 000 men and 1 619 000 women) avoided deaths for all neoplasms over the period 1989–2021 and 348 000 (246 000 men and 102 000 women) in 2021 alone in the EU27. For both sexes, we estimated 1 679 000 avoided deaths for stomach cancer, 747 000 for colorectum, 227 000 for bladder, 102 000 for leukemias. Avoided deaths for lung cancer accounted for 1 156 000 in men, while no reduction was estimated for women. For breast and uterine cancer, avoided deaths were about 300 000, for ovary 105 000 and for prostate 352 000. In the UK, a total of 1 061 000 (721 000 men and 340 000 women) deaths was avoided. Elimination of tobacco may avoid a further 20% of cancer mortality by 2050. Control of alcohol, overweight and obesity, and occupational and environmental carcinogens may avoid an additional 10% of cancer deaths. A similar reduction may be due to optimal adoption of cervical, colorectal, breast, and probably, lung and prostate cancer screening. Thus, primary and secondary cancer prevention can avoid an additional third of cancer deaths in Europe up to 2050.